subject:(Protein ligand Interactions)

University of Texas – Austin

1. Farley, Christopher Alexander. Design, synthesis, and thermodynamic evaluation of peptidomimetic ligands binding to the Src SH2 domain.

Degree: MA, Chemistry, 2018, University of Texas – Austin

URL: http://hdl.handle.net/2152/68037

► The ability to predict protein-ligand binding affinities is a difficult and elusive goal in the field of molecular recognition. Models exist to predict binding energetics;… (more)

Subjects/Keywords: Protein-ligand interactions; Protein-ligand binding; Ligand preorganization

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APA (6^th Edition):

Farley, C. A. (2018). Design, synthesis, and thermodynamic evaluation of peptidomimetic ligands binding to the Src SH2 domain. (Masters Thesis). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/68037

Chicago Manual of Style (16^th Edition):

Farley, Christopher Alexander. “Design, synthesis, and thermodynamic evaluation of peptidomimetic ligands binding to the Src SH2 domain.” 2018. Masters Thesis, University of Texas – Austin. Accessed January 23, 2021. http://hdl.handle.net/2152/68037.

MLA Handbook (7^th Edition):

Farley, Christopher Alexander. “Design, synthesis, and thermodynamic evaluation of peptidomimetic ligands binding to the Src SH2 domain.” 2018. Web. 23 Jan 2021.

Vancouver:

Farley CA. Design, synthesis, and thermodynamic evaluation of peptidomimetic ligands binding to the Src SH2 domain. [Internet] [Masters thesis]. University of Texas – Austin; 2018. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/2152/68037.

Council of Science Editors:

Farley CA. Design, synthesis, and thermodynamic evaluation of peptidomimetic ligands binding to the Src SH2 domain. [Masters Thesis]. University of Texas – Austin; 2018. Available from: http://hdl.handle.net/2152/68037

University of California – San Francisco

2. Cruz, Leslie Ann. Studies in Structure, Chemistry & Biology Of Receptor-Ligand Interactions for the AMPA & Androgen Receptors.

Degree: Chemistry and Chemical Biology, 2011, University of California – San Francisco

URL: http://www.escholarship.org/uc/item/267353tc

► Numerous small molecules serve to coordinate many biological activities within cells of multicelluar organisms. These ligand-receptor interactions are vital to the control of cellular processes… (more)

Subjects/Keywords: Chemistry; Biophysics; Biochemistry; chemical biology; protein engineering; protein-ligand interactions

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APA (6^th Edition):

Cruz, L. A. (2011). Studies in Structure, Chemistry & Biology Of Receptor-Ligand Interactions for the AMPA & Androgen Receptors. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/267353tc

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cruz, Leslie Ann. “Studies in Structure, Chemistry & Biology Of Receptor-Ligand Interactions for the AMPA & Androgen Receptors.” 2011. Thesis, University of California – San Francisco. Accessed January 23, 2021. http://www.escholarship.org/uc/item/267353tc.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cruz, Leslie Ann. “Studies in Structure, Chemistry & Biology Of Receptor-Ligand Interactions for the AMPA & Androgen Receptors.” 2011. Web. 23 Jan 2021.

Vancouver:

Cruz LA. Studies in Structure, Chemistry & Biology Of Receptor-Ligand Interactions for the AMPA & Androgen Receptors. [Internet] [Thesis]. University of California – San Francisco; 2011. [cited 2021 Jan 23]. Available from: http://www.escholarship.org/uc/item/267353tc.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cruz LA. Studies in Structure, Chemistry & Biology Of Receptor-Ligand Interactions for the AMPA & Androgen Receptors. [Thesis]. University of California – San Francisco; 2011. Available from: http://www.escholarship.org/uc/item/267353tc

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Hong Kong University of Science and Technology

3. Gu, Shuo. Computational exploration of protein ligand interaction and its applications in drug discovery.

Degree: 2015, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-80261 ; https://doi.org/10.14711/thesis-b1514980 ; http://repository.ust.hk/ir/bitstream/1783.1-80261/1/th_redirect.html

► My PhD research can be summarized as two major directions. One direction is the theoretical investigation of protein conformational dynamics. In particular, we have developed… (more)

Subjects/Keywords: Protein-protein interactions ; Computer simulation ; Ligand binding (Biochemistry) ; Drugs ; Design

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APA (6^th Edition):

Gu, S. (2015). Computational exploration of protein ligand interaction and its applications in drug discovery. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-80261 ; https://doi.org/10.14711/thesis-b1514980 ; http://repository.ust.hk/ir/bitstream/1783.1-80261/1/th_redirect.html

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gu, Shuo. “Computational exploration of protein ligand interaction and its applications in drug discovery.” 2015. Thesis, Hong Kong University of Science and Technology. Accessed January 23, 2021. http://repository.ust.hk/ir/Record/1783.1-80261 ; https://doi.org/10.14711/thesis-b1514980 ; http://repository.ust.hk/ir/bitstream/1783.1-80261/1/th_redirect.html.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gu, Shuo. “Computational exploration of protein ligand interaction and its applications in drug discovery.” 2015. Web. 23 Jan 2021.

Vancouver:

Gu S. Computational exploration of protein ligand interaction and its applications in drug discovery. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2015. [cited 2021 Jan 23]. Available from: http://repository.ust.hk/ir/Record/1783.1-80261 ; https://doi.org/10.14711/thesis-b1514980 ; http://repository.ust.hk/ir/bitstream/1783.1-80261/1/th_redirect.html.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gu S. Computational exploration of protein ligand interaction and its applications in drug discovery. [Thesis]. Hong Kong University of Science and Technology; 2015. Available from: http://repository.ust.hk/ir/Record/1783.1-80261 ; https://doi.org/10.14711/thesis-b1514980 ; http://repository.ust.hk/ir/bitstream/1783.1-80261/1/th_redirect.html

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Hong Kong University of Science and Technology

4. Chan, King Hang LIFS. The molecular basis of ligand selectivity and functional specificity of melatonin receptor subtypes.

Degree: 2015, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-97093 ; https://doi.org/10.14711/thesis-b1585311 ; http://repository.ust.hk/ir/bitstream/1783.1-97093/1/th_redirect.html

► MT₁ and MT₂ melatonin receptors are expressed throughout the body and regulate an immense diversity of physiological processes. While the melatonin receptor subtypes may work… (more)

Subjects/Keywords: Melatonin ; Receptors ; Ligand binding (Biochemistry) ; Protein-protein interactions

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APA (6^th Edition):

Chan, K. H. L. (2015). The molecular basis of ligand selectivity and functional specificity of melatonin receptor subtypes. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-97093 ; https://doi.org/10.14711/thesis-b1585311 ; http://repository.ust.hk/ir/bitstream/1783.1-97093/1/th_redirect.html

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chan, King Hang LIFS. “The molecular basis of ligand selectivity and functional specificity of melatonin receptor subtypes.” 2015. Thesis, Hong Kong University of Science and Technology. Accessed January 23, 2021. http://repository.ust.hk/ir/Record/1783.1-97093 ; https://doi.org/10.14711/thesis-b1585311 ; http://repository.ust.hk/ir/bitstream/1783.1-97093/1/th_redirect.html.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chan, King Hang LIFS. “The molecular basis of ligand selectivity and functional specificity of melatonin receptor subtypes.” 2015. Web. 23 Jan 2021.

Vancouver:

Chan KHL. The molecular basis of ligand selectivity and functional specificity of melatonin receptor subtypes. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2015. [cited 2021 Jan 23]. Available from: http://repository.ust.hk/ir/Record/1783.1-97093 ; https://doi.org/10.14711/thesis-b1585311 ; http://repository.ust.hk/ir/bitstream/1783.1-97093/1/th_redirect.html.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chan KHL. The molecular basis of ligand selectivity and functional specificity of melatonin receptor subtypes. [Thesis]. Hong Kong University of Science and Technology; 2015. Available from: http://repository.ust.hk/ir/Record/1783.1-97093 ; https://doi.org/10.14711/thesis-b1585311 ; http://repository.ust.hk/ir/bitstream/1783.1-97093/1/th_redirect.html

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University

5. Allison, Brittany Ann. Computational Design of Protein-Ligand Interfaces Using RosettaLigand.

Degree: PhD, Chemistry, 2016, Vanderbilt University

URL: http://hdl.handle.net/1803/11616

► Computational design of protein-ligand interfaces expands understanding of the basic forces involved in molecular recognition, and also contributes to the development of protein therapeutics. My… (more)

▼ Computational design of protein-ligand interfaces expands understanding of the basic forces involved in molecular recognition, and also contributes to the development of protein therapeutics. My dissertation research contributes to this body of knowledge through a series of Specific Aims. Specific Aim 1 involves screening a diverse set of small molecules for intrinsic binding affinity to my protein, HisF. 28 binding ligands were identified by using nuclear magnetic resonance (NMR) techniques by tracking chemical shift peaks. This also allows us to calculation dissociation constants, which ranged between 340 – 1110 µM. These binding ligands were then computationally docked into HisF using RosettaLigand of the Rosetta modeling suite. Computational results were compared to the experimental data to identify strengths/weaknesses of the program. These results are the focus of Chapter 3, “Experimental and Computational Identification of Naïve Binders to a TIM-Barrel Protein Scaffold” (first author), to be submitted soon. Specific Aim 2 involved optimizing RosettaLigand to design proteins that bind small molecules. The software was tested for accuracy and efficiency using a set of protein-ligand crystal structures, and these results are the focus of my 2014 published manuscript and Chapter 2, “Computational Design of Protein-Small Molecule Interfaces” (first author). A detailed description of how to utilize RosettaLigand is the focus of Chapter 4, “Rosetta and Design of Ligand Binding Sites” (secondary author), manuscript accepted. Specific Aim 3 combines the first two aims, to redesign the protein interface to bind the small molecules more tightly than the wild type protein. We have used RosettaLigand to redesign HisF to bind one VU0068924 more tightly, with binding affinity improving from 442 µM to 23 µM. This is the focus of Appendix C “Designed C9S_HisF Binds VU0068924 More Tightly”, and will be the focus of a future manuscript. For each project, the protocols, scripts, command-lines, experiments not described in the manuscript are included in the appendix. The models, code, scripts, and figures are included in the thesis directory that accompanies the thesis. Advisors/Committee Members: Brian O. Bachmann, Ph.D. (committee member), Michael P. Stone, PhD. (committee member), John A. Capra, Ph.D. (committee member), Jens Meiler, Ph.D. (Committee Chair).

Subjects/Keywords: protein engineering; protein ligand binding; RosettaLigand; Rosetta; protein small molecule interactions; interface design; computational design; ligand macromolecule recognition; NMR; binding affinity

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APA (6^th Edition):

Allison, B. A. (2016). Computational Design of Protein-Ligand Interfaces Using RosettaLigand. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/11616

Chicago Manual of Style (16^th Edition):

Allison, Brittany Ann. “Computational Design of Protein-Ligand Interfaces Using RosettaLigand.” 2016. Doctoral Dissertation, Vanderbilt University. Accessed January 23, 2021. http://hdl.handle.net/1803/11616.

MLA Handbook (7^th Edition):

Allison, Brittany Ann. “Computational Design of Protein-Ligand Interfaces Using RosettaLigand.” 2016. Web. 23 Jan 2021.

Vancouver:

Allison BA. Computational Design of Protein-Ligand Interfaces Using RosettaLigand. [Internet] [Doctoral dissertation]. Vanderbilt University; 2016. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1803/11616.

Council of Science Editors:

Allison BA. Computational Design of Protein-Ligand Interfaces Using RosettaLigand. [Doctoral Dissertation]. Vanderbilt University; 2016. Available from: http://hdl.handle.net/1803/11616

University of Edinburgh

6. Calabrò, Gaetano. Accelerating molecular simulations : implication for rational drug design.

Degree: PhD, 2015, University of Edinburgh

URL: http://hdl.handle.net/1842/16439

► The development and approval of new drugs is an expensive process. The total cost for the approval of a new compound is on average 1.0… (more)

▼ The development and approval of new drugs is an expensive process. The total cost for the approval of a new compound is on average 1.0 - 1.2 billion dollars and the entire process lasts about 12 - 15 years. The main difficulties are related to poor pharmacokinetics, lack of efficacy and unwanted side effects. These problems have naturally led to the question if new and alternative methodologies can be developed to find reliable and low cost alternatives to existing practices. Nowadays, computer-assisted tools are used to support the decision process along the early stages of the drug discovery path leading from the identification of a suitable biomolecular target to the design/optimization of drug-like molecules. This process includes assessments about target druggability, screening of molecular libraries and the optimization of lead compounds where new drug-like molecules able to bind with sufficiently affinity and specificity to a disease-involved protein are designed. Existing computational methods used by the pharmaceutical industry are usually focused on the screening of library compounds such as docking, chemoinformatics and other ligand-based methods to predict and improve binding affinities, but their reliable application requires improvements in accuracy. New quantitative methods based on molecular simulations of drug binding to a protein could greatly improve prospects for the reliable in-silico design of new potent drug candidates. A common parameter used by medicinal chemists to quantify the affinity between candidate ligands and a target protein is represented by the free energy of binding. However, despite the increased amount of structural information, predicting binding free energy is still a challenge and this technique has found limited use beyond academia. A major reason for limited adoption in the industry is that reliable computer models of drug binding to a protein must reproduce the change in molecular conformations of the drug and protein upon complex formation and this includes the correct modelling of weak non-covalent interactions such as hydrogen bonds, burials of hydrophobic surface areas, Van der Waals interactions, fixations of molecular degrees of freedom solvation/desolvation of polar groups and different entropy contributions related to the solvent and protein interactions. For several classes of proteins these phenomena are not easy to model and often require extremely computationally intensive simulations. The main goal of the thesis was to explore efficient ways of computing binding affinities by using molecular simulations. With this aim, novel software to compute relative binding free energies has been developed. The implementation is based on alchemical transformations and it extended a preexisted piece of software Sire, a molecular modeling framework, by using the OpenMM APIs to run fast molecular dynamics simulations on the latest GPGPU technology. This new piece of software has equipped the scientific community with a flexible and fast tool, not only to predict relative…

Subjects/Keywords: 615.1; protein-ligand interactions; non additivity; alchemical free energy calculations

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APA (6^th Edition):

Calabrò, G. (2015). Accelerating molecular simulations : implication for rational drug design. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/16439

Chicago Manual of Style (16^th Edition):

Calabrò, Gaetano. “Accelerating molecular simulations : implication for rational drug design.” 2015. Doctoral Dissertation, University of Edinburgh. Accessed January 23, 2021. http://hdl.handle.net/1842/16439.

MLA Handbook (7^th Edition):

Calabrò, Gaetano. “Accelerating molecular simulations : implication for rational drug design.” 2015. Web. 23 Jan 2021.

Vancouver:

Calabrò G. Accelerating molecular simulations : implication for rational drug design. [Internet] [Doctoral dissertation]. University of Edinburgh; 2015. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1842/16439.

Council of Science Editors:

Calabrò G. Accelerating molecular simulations : implication for rational drug design. [Doctoral Dissertation]. University of Edinburgh; 2015. Available from: http://hdl.handle.net/1842/16439

Indian Institute of Science

7. Dighe, Anasuya. Studies on Dynamic Plasticity of Ligand Binding Sites in Proteins.

Degree: PhD, Faculty of Science, 2019, Indian Institute of Science

URL: http://etd.iisc.ac.in/handle/2005/4236

► Molecular recognition between proteins and their associated ligands constitutes ligand-induced protein rewiring thereby enabling the formation of a stable protein-ligand complex. The studies presented in… (more)

▼ Molecular recognition between proteins and their associated ligands constitutes ligand-induced protein rewiring thereby enabling the formation of a stable protein-ligand complex. The studies presented in this thesis address the conformational plasticity inherent to proteins by virtue of which they adapt to diverse ligands and orchestrate complex biological processes like signal transduction, transcription and protein-protein interaction. Adopting network theory based formalisms for understanding protein-ligand associations involve deconstructing the three-dimensional structure of a protein in terms of nodes and edges. With this view, Protein Structure Networks (PSNs) of ligand-bound complexes are studied by considering their side-chain non-covalent interactions. Agonist and antagonist-bound G-Protein Coupled Receptors (GPCRs) are investigated to gain mechanistic insights into allostery and its role in signal transduction. The degree of similarity between PSNs of these complexes is quantified by means of Network Similarity Score (NSS). The physical nature of these networks is inspected by subjecting them to perturbations and major players in maintaining the stability of such networks are identified. Residue-wise groupings (at backbone and side-chain level) are obtained by applying graph spectral methods. All-atom Molecular Dynamics (MD) simulations are carried out to gain a better understanding of protein-ligand binding by analysing conformational ensembles of these complexes. In this scenario, two members from a highly versatile ligand-inducible transcription factor superfamily, i.e., Nuclear Receptors (NR) are studied, that are known to exhibit extremes of ligand binding behavior ranging from promiscuity to specificity. Diverse ligands are known to bind to proteins and the overall nature of their binding site is investigated. In particular, similarities among binding sites of diverse proteins are analysed by using PocketMatch. Percolation of these similarities to regions surrounding the binding site is reported and examples depicting this extended similarity are discussed. Overall, studies presented in this thesis provide a structural perspective into the adaptability of proteins for recognizing diverse ligands and undergoing local or global re-organizations in their framework to regulate complex biological processes. Advisors/Committee Members: Vishveshwara, Saraswathi (advisor), Chandra, Nagasuma (advisor).

Subjects/Keywords: Protein-ligand Interactions; Protein Ligand Interactions; Protein Structure Networks (PSNs); Graph Theory; Protein Side-chain Networks (PScN); Muscarinic Acetylcholine Receptors; Muscarinic Receptor Cmplexes; Protein-Protein Interactions; Pregnane X Receptor; G-Protein Coupled Receptors (GPCRs); Network Similarity Score (NSS); Biochemistry

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dighe, A. (2019). Studies on Dynamic Plasticity of Ligand Binding Sites in Proteins. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/4236

Chicago Manual of Style (16^th Edition):

Dighe, Anasuya. “Studies on Dynamic Plasticity of Ligand Binding Sites in Proteins.” 2019. Doctoral Dissertation, Indian Institute of Science. Accessed January 23, 2021. http://etd.iisc.ac.in/handle/2005/4236.

MLA Handbook (7^th Edition):

Dighe, Anasuya. “Studies on Dynamic Plasticity of Ligand Binding Sites in Proteins.” 2019. Web. 23 Jan 2021.

Vancouver:

Dighe A. Studies on Dynamic Plasticity of Ligand Binding Sites in Proteins. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2019. [cited 2021 Jan 23]. Available from: http://etd.iisc.ac.in/handle/2005/4236.

Council of Science Editors:

Dighe A. Studies on Dynamic Plasticity of Ligand Binding Sites in Proteins. [Doctoral Dissertation]. Indian Institute of Science; 2019. Available from: http://etd.iisc.ac.in/handle/2005/4236

8. Aguirre, Clémentine. Analyse quantitative des perturbations de déplacement chimique pour la détermination de structures tridimensionnelles de complexes protéine-ligand : Quantitative analysis of chemical shift perturbations for the determination of protein-ligand complex tridimentional structures.

Degree: Docteur es, Chimie analytique, 2014, Université Claude Bernard – Lyon I

URL: http://www.theses.fr/2014LYO10217

►

Les interactions intermoléculaires entre une protéine et ses différents partenaires représentent des cibles de plus en plus prisées pour l'élaboration de composés thérapeutiques capables d'intervenir… (more)

▼

Les interactions intermoléculaires entre une protéine et ses différents partenaires représentent des cibles de plus en plus prisées pour l'élaboration de composés thérapeutiques capables d'intervenir dans des processus biologiques. La méthode FBDD (Fragment-Based Drug Design) permet de concevoir des molécules bioactives tels que des inhibiteurs, à partir de la structure tridimensionnelle du complexe formé entre la protéine et une molécule fragment. Dans le cadre de ce projet de thèse nous proposons d'utiliser le déplacement chimique pour l'étude des structures 3D de ces complexes protéine-ligand. Nous nous focaliserons sur la mesure des perturbations de déplacement chimique CSP (Chemical Shift Perturbations) des atomes d'une protéine cible, induites par la liaison d'un fragment. Nous démontrerons la puissance de cet outil RMN à travers la simulation des CSP induits par l'interaction d'un fragment sur une protéine cible et leur comparaison aux CSP expérimentaux. L'analyse sera réalisée sur deux protéines cibles et la comparaison des données expérimentales et simulées permettra dans un premier temps de mettre en évidence un réarrangement structural de la protéine Bcl-xL lors de son interaction avec un fragment. Puis, dans un second temps, nous montrerons que cette analyse quantitative des CSP peut permettre de déterminer l'orientation des fragments dans le site d'interaction de la protéine PRDX5. Nous comparerons alors les performances de la méthode pour différents types de protons proposant ainsi de nouvelles pistes pour la compréhension du comportement des CSP vis-à-vis de leurs contributions électroniques

Intermolecular interactions between protein and its partners represent highly attractive targets for the elaboration of therapeutic compounds abble to interfere in biological processes. A novel approach in drug design called Fragment-Based Drug Design (FBDD) consists of designing bioactive molecules like inhibitors, from the 3D structure of the complex formed between a protein and a fragment molecule (MW < 300g/mol). Here we suggest using the chemical shift, to study these protein-ligand structures. We will particularly focus on the measurement of Chemical Shift Perturbations (CSP) induced by the fragment-binding on protein’s nuclei. We will evidence the potency of this NMR tool through simulation of CSP induced by fragment interaction on protein target and the comparison with experimental CSP. Two protein targets will be used and the comparison between experimental and simulated data will evidence on one hand, the structural rearrangement of the protein Bcl-xL upon fragment-binding. On the other hand, we will demonstrate that this quantitative use of CSP is unable to determinate fragment orientations inside the protein PRDX5 binding site. We will compare the performances of the method for different kinds of protein and proposing answers to better understand the behaviour of CSP toward their different electronic contributions

Advisors/Committee Members: Krimm, Isabelle (thesis director).

Subjects/Keywords: Perturbations de déplacement chimique; Fragments; Interaction protéine-ligand; RMN; Chemical Shift Perturbations; Fragments; Protein-ligand interactions; NMR; 543

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APA (6^th Edition):

Aguirre, C. (2014). Analyse quantitative des perturbations de déplacement chimique pour la détermination de structures tridimensionnelles de complexes protéine-ligand : Quantitative analysis of chemical shift perturbations for the determination of protein-ligand complex tridimentional structures. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2014LYO10217

Chicago Manual of Style (16^th Edition):

Aguirre, Clémentine. “Analyse quantitative des perturbations de déplacement chimique pour la détermination de structures tridimensionnelles de complexes protéine-ligand : Quantitative analysis of chemical shift perturbations for the determination of protein-ligand complex tridimentional structures.” 2014. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed January 23, 2021. http://www.theses.fr/2014LYO10217.

MLA Handbook (7^th Edition):

Aguirre, Clémentine. “Analyse quantitative des perturbations de déplacement chimique pour la détermination de structures tridimensionnelles de complexes protéine-ligand : Quantitative analysis of chemical shift perturbations for the determination of protein-ligand complex tridimentional structures.” 2014. Web. 23 Jan 2021.

Vancouver:

Aguirre C. Analyse quantitative des perturbations de déplacement chimique pour la détermination de structures tridimensionnelles de complexes protéine-ligand : Quantitative analysis of chemical shift perturbations for the determination of protein-ligand complex tridimentional structures. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2014. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2014LYO10217.

Council of Science Editors:

Aguirre C. Analyse quantitative des perturbations de déplacement chimique pour la détermination de structures tridimensionnelles de complexes protéine-ligand : Quantitative analysis of chemical shift perturbations for the determination of protein-ligand complex tridimentional structures. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2014. Available from: http://www.theses.fr/2014LYO10217

University of Ottawa

9. Sun, Jiayin. The Structural Basis for Lipid-Dependent Uncoupling of the Nicotinic Acetylcholine Receptor .

Degree: 2017, University of Ottawa

URL: http://hdl.handle.net/10393/35642

► In lipid membranes lacking activating lipids, the nicotinic acetylcholine receptor adopts an uncoupled conformation that binds ligand, but does not transition into an open conformation.… (more)

Subjects/Keywords: Structure; Lipid-protein interactions; Mechanism; Nicotinic acetylcholine receptor; Uncoupling; ELIC; Pentameric ligand-gated ion channels

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APA (6^th Edition):

Sun, J. (2017). The Structural Basis for Lipid-Dependent Uncoupling of the Nicotinic Acetylcholine Receptor . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/35642

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sun, Jiayin. “The Structural Basis for Lipid-Dependent Uncoupling of the Nicotinic Acetylcholine Receptor .” 2017. Thesis, University of Ottawa. Accessed January 23, 2021. http://hdl.handle.net/10393/35642.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sun, Jiayin. “The Structural Basis for Lipid-Dependent Uncoupling of the Nicotinic Acetylcholine Receptor .” 2017. Web. 23 Jan 2021.

Vancouver:

Sun J. The Structural Basis for Lipid-Dependent Uncoupling of the Nicotinic Acetylcholine Receptor . [Internet] [Thesis]. University of Ottawa; 2017. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10393/35642.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sun J. The Structural Basis for Lipid-Dependent Uncoupling of the Nicotinic Acetylcholine Receptor . [Thesis]. University of Ottawa; 2017. Available from: http://hdl.handle.net/10393/35642

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Lund

10. Peterson, Kristoffer. Molecular basis for galectin-ligand interactions : Design, synthesis and analysis of ligands.

Degree: 2018, University of Lund

URL: https://lup.lub.lu.se/record/777b2fa7-2293-453b-9771-0f0ab6f6a6d2 ; https://portal.research.lu.se/ws/files/38414625/Thesis.pdf

► Galectins are a class of β-galactoside-binding proteins that bind glycoconjugates and have been implicated in cancer, regulation of immunity and inflammation. Design and synthesis have… (more)

Subjects/Keywords: Organic Chemistry; Galectin; Structure-based design; Thiodigalactoside; Huisgen 1,3-dipolar cycloaddition; Protein-ligand binding interactions

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APA (6^th Edition):

Peterson, K. (2018). Molecular basis for galectin-ligand interactions : Design, synthesis and analysis of ligands. (Doctoral Dissertation). University of Lund. Retrieved from https://lup.lub.lu.se/record/777b2fa7-2293-453b-9771-0f0ab6f6a6d2 ; https://portal.research.lu.se/ws/files/38414625/Thesis.pdf

Chicago Manual of Style (16^th Edition):

Peterson, Kristoffer. “Molecular basis for galectin-ligand interactions : Design, synthesis and analysis of ligands.” 2018. Doctoral Dissertation, University of Lund. Accessed January 23, 2021. https://lup.lub.lu.se/record/777b2fa7-2293-453b-9771-0f0ab6f6a6d2 ; https://portal.research.lu.se/ws/files/38414625/Thesis.pdf.

MLA Handbook (7^th Edition):

Peterson, Kristoffer. “Molecular basis for galectin-ligand interactions : Design, synthesis and analysis of ligands.” 2018. Web. 23 Jan 2021.

Vancouver:

Peterson K. Molecular basis for galectin-ligand interactions : Design, synthesis and analysis of ligands. [Internet] [Doctoral dissertation]. University of Lund; 2018. [cited 2021 Jan 23]. Available from: https://lup.lub.lu.se/record/777b2fa7-2293-453b-9771-0f0ab6f6a6d2 ; https://portal.research.lu.se/ws/files/38414625/Thesis.pdf.

Council of Science Editors:

Peterson K. Molecular basis for galectin-ligand interactions : Design, synthesis and analysis of ligands. [Doctoral Dissertation]. University of Lund; 2018. Available from: https://lup.lub.lu.se/record/777b2fa7-2293-453b-9771-0f0ab6f6a6d2 ; https://portal.research.lu.se/ws/files/38414625/Thesis.pdf

Indian Institute of Science

11. Bhattacharyya, Moitrayee. Probing Ligand Induced Perturbations In Protien Structure Networks : Physico-Chemical Insights From MD Simulations And Graph Theory.

Degree: PhD, Faculty of Science, 2014, Indian Institute of Science

URL: http://etd.iisc.ac.in/handle/2005/2341

► The fidelity of biological processes and reactions, inspite of the widespread diversity, is programmed by highly specific physico-chemical principles. This underlines our basic understanding of… (more)

▼ The fidelity of biological processes and reactions, inspite of the widespread diversity, is programmed by highly specific physico-chemical principles. This underlines our basic understanding of different interesting phenomena of biological relevance, ranging from enzyme specificity to allosteric communication, from selection of fold to structural organization / states of oligomerization, from half-sites-reactivity to reshuffling of the conformational free energy landscape, encompassing the dogma of sequence-structure dynamics-function of macromolecules. The role of striking an optimal balance between rigidity and flexibility in macromolecular 3D structural organisation is yet another concept that needs attention from the functional perspective. Needless to say that the variety of protein structures and conformations naturally leads to the diversity of their function and consequently many other biological functions in general. Classical models of allostery like the ‘MWC model’ or the ‘KNF model’ and the more recently proposed ‘population shift model’ have advanced our understanding of the underlying principles of long range signal transfer in macromolecules. Extensive studies have also reported the importance of the fold selection and 3D structural organisation in the context of macromolecular function. Also ligand induced conformational changes in macromolecules, both subtle and drastic, forms the basis for controlling several biological processes in an ordered manner by re-organizing the free energy landscape. The above mentioned biological phenomena have been observed from several different biochemical and biophysical approaches. Although these processes may often seem independent of each other and are associated with regulation of specialized functions in macromolecules, it is worthwhile to investigate if they share any commonality or interdependence at the detailed atomic level of the 3D structural organisation. So the nagging question is, do these diverse biological processes have a unifying theme, when probed at a level that takes into account even subtle re-orchestrations of the interactions and energetics at the protein/nucleic acid side-chain level. This is a complex problem to address and here we have made attempts to examine this problem using computational tools. Two methods have been extensively applied: Molecular Dynamics (MD) simulations and network theory and related parameters. Network theory has been extensively used in the past in several studies, ranging from analysis of social networks to systems level networks in biology (e.g., metabolic networks) and have also found applications in the varied fields of physics, economics, cartography and psychology. More recently, this concept has been applied to study the intricate details of the structural organisation in proteins, providing a local view of molecular interactions from a global perspective. On the other hand, MD simulations capture the dynamics of interactions and the conformational space associated with a given state (e.g., different… Advisors/Committee Members: Vishveshwara, Saraswathi (advisor).

Subjects/Keywords: Protein Structure; Protein - Non Covalent Interactions; Nucleic Acids- Non Covalent Interactions; Bacterial LuxS Protein; Protein-Ligand Interactions; Protein Structure Networks; Proteins - Conformation; Allosteric Proteins; Energy-Weighted Network Formalism; Proteins - Allosterism; Protein Structure Network (PSN); Protein Structure Graph (PSN); Protein Complex Energy Network (PcEN); Biochemistry

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bhattacharyya, M. (2014). Probing Ligand Induced Perturbations In Protien Structure Networks : Physico-Chemical Insights From MD Simulations And Graph Theory. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/2341

Chicago Manual of Style (16^th Edition):

Bhattacharyya, Moitrayee. “Probing Ligand Induced Perturbations In Protien Structure Networks : Physico-Chemical Insights From MD Simulations And Graph Theory.” 2014. Doctoral Dissertation, Indian Institute of Science. Accessed January 23, 2021. http://etd.iisc.ac.in/handle/2005/2341.

MLA Handbook (7^th Edition):

Bhattacharyya, Moitrayee. “Probing Ligand Induced Perturbations In Protien Structure Networks : Physico-Chemical Insights From MD Simulations And Graph Theory.” 2014. Web. 23 Jan 2021.

Vancouver:

Bhattacharyya M. Probing Ligand Induced Perturbations In Protien Structure Networks : Physico-Chemical Insights From MD Simulations And Graph Theory. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2014. [cited 2021 Jan 23]. Available from: http://etd.iisc.ac.in/handle/2005/2341.

Council of Science Editors:

Bhattacharyya M. Probing Ligand Induced Perturbations In Protien Structure Networks : Physico-Chemical Insights From MD Simulations And Graph Theory. [Doctoral Dissertation]. Indian Institute of Science; 2014. Available from: http://etd.iisc.ac.in/handle/2005/2341

Rhodes University

12. Penkler, David Lawrence. In silico analysis of human Hsp90 for the identification of novel anti-cancer drug target sites and natural compound inhibitors.

Degree: Faculty of Science, Biochemistry and Microbiology, 2015, Rhodes University

URL: http://hdl.handle.net/10962/d1018938

► The 90-KDa heat shock protein (Hsp90) is part of the molecular chaperone family, and as such it is involved in the regulation of protein homeostasis… (more)

▼ The 90-KDa heat shock protein (Hsp90) is part of the molecular chaperone family, and as such it is involved in the regulation of protein homeostasis within cells. Specifically, Hsp90 aids in the folding of nascent proteins and re-folding of denatured proteins. It also plays an important role in the prevention of protein aggregation. Hsp90’s functionality is attributed to its several staged, multi-conformational ATPase cycle, in which associated client proteins are bound and released. Hsp90 is known to be associated with a wide array of client proteins, some of which are thought to be involved in multiple oncogenic processes. Indeed Hsp90 is known to be directly involved in perpetuating the stability and function of multiple mutated, chimeric and over-expressed signalling proteins that are known to promote the growth and survival of cancer cells. Hsp90 inhibitors are thus thought to be promising therapeutic agents for cancer treatment. A lack of a 3D structure of human Hsp90 however has restricted Hsp90 inhibitor development in large to in vivo investigations. This study, aims to investigate and calculate hypothetical homology models of the full human Hsp90 protein, and to probe these structural models for novel drug target sites using several in silico techniques. A multi-template homology modelling methodology was developed and in conjunction with protein-protein docking techniques, two functionally important human Hsp90 structural models were calculated; the nucleotide free “v-like” open and nucleotide bound closed conformations. Based on the conservation of ligand binding, virtual screening experiments conducted on both models using 316 natural compounds indigenous to South Africa, revealed three novel putative target sites. Two binding pockets in close association with important Hsp90-Hop interaction residues and a single binding pocket on the dimerization interface in the C-terminal domain. Targeted molecular docking experiments at these sites revealed two compounds (721395-11-5 and 264624-39-7) as putative inhibitors, both showing strong binding affinities for at least one of the three investigated target sites. Furthermore both compounds were found to only violate one Lipinski’s rules, suggesting their potential as candidates for further drug development. The combined work described here provides a putative platform for the development of next generation inhibitors of human Hsp90.

Subjects/Keywords: Heat shock proteins; Cancer – Treatment; Molecular chaperones; Homeostasis; Carcinogenesis; Chemotherapy; Ligand binding (Biochemistry); Protein-protein interactions

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APA (6^th Edition):

Penkler, D. L. (2015). In silico analysis of human Hsp90 for the identification of novel anti-cancer drug target sites and natural compound inhibitors. (Thesis). Rhodes University. Retrieved from http://hdl.handle.net/10962/d1018938

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Penkler, David Lawrence. “In silico analysis of human Hsp90 for the identification of novel anti-cancer drug target sites and natural compound inhibitors.” 2015. Thesis, Rhodes University. Accessed January 23, 2021. http://hdl.handle.net/10962/d1018938.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Penkler, David Lawrence. “In silico analysis of human Hsp90 for the identification of novel anti-cancer drug target sites and natural compound inhibitors.” 2015. Web. 23 Jan 2021.

Vancouver:

Penkler DL. In silico analysis of human Hsp90 for the identification of novel anti-cancer drug target sites and natural compound inhibitors. [Internet] [Thesis]. Rhodes University; 2015. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10962/d1018938.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Penkler DL. In silico analysis of human Hsp90 for the identification of novel anti-cancer drug target sites and natural compound inhibitors. [Thesis]. Rhodes University; 2015. Available from: http://hdl.handle.net/10962/d1018938

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

13. Planesas Galvez, Jesús M. Estudio y cribado virtual de compuestos químicos antivirales (VIH). Estudio de la modulación alostérica de agonistas y antagonistas del receptor celular CXCR4.

Degree: 2015, Universitat Ramon Llull

URL: http://hdl.handle.net/10803/312147

► : Drug discovery methods have recently emerged thanks to the resolution of protein structures which act as therapeutic targets responsible for diseases or biological deregulations.… (more)

▼ : Drug discovery methods have recently emerged thanks to the resolution of protein structures which act as therapeutic targets responsible for diseases or biological deregulations. These three dimensional structures in combination with the development of new computational techniques are accelerating the development of new candidates to become drug compounds. This work starts with the proposal of a new method that improves the selection of candidates to become inhibitors of a well-known “difficult target” such us VEGFR-2 receptor. This method is based on the crystal structure of the receptor and also by a number of inhibitors known for this target. CXCR4 crystal structure was solved in 2010 by X-ray crystallography and this has been an important event in order to improve the molecular design of HIV inhibitors, as well as anticancer compounds, diseases where CXCR4 receptor is involved. Therefore, virtual screening models developed in the laboratory of molecular design of IQS (GEM) were generated using homology models from other GPCRs and/or based on ligand shape techniques. In this sense, taking into consideration all published CXCR4 crystal structures, it has been evaluated which of them shows the most suitable conformation to distinguish antagonists actives from inactives. Moreover, different virtual screening methods have also been evaluated such us structure based methods, ligand based methods and pharmacophoric models. Once obtained the most suitable structure and the best retrospective virtual screening methods, a prospective virtual screening has been carried out using a new combinatorial library of chemical structures. This new library is based on analogous structures previously generated in the laboratory of molecular design of IQS (GEM). In addition, the allosteric behaviour of CXCR4 receptor has been studied versus small antagonist modulators and versus peptidomimetic agonist modulators. CXCR4 is classified as a “difficult target” due to the large size of its extracellular pocket that the orthosteric binding site is placed as well as the diverse number of biochemical regulations where the receptor mediates. Thus, the allosteric modulation of CXCR4 has been studied using different approaches such as blind docking, protein-protein docking, docking by subsites and molecular dynamics. Advisors/Committee Members: Universitat Ramon Llull. IQS - Química Orgànica, [email protected] (authoremail), true (authoremailshow), Teixidó Closa, Jordi (director), Pérez Nueno, Violeta Isabel (codirector), true (authorsendemail).

Subjects/Keywords: Allosterism; CXCR4; Docking; Peptide-protein docking; Molecular dynamics; Pharmacophore; Protein-ligand interactions; Tanimoto; Ciències; 547; 577

10 more images…

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APA (6^th Edition):

Planesas Galvez, J. M. (2015). Estudio y cribado virtual de compuestos químicos antivirales (VIH). Estudio de la modulación alostérica de agonistas y antagonistas del receptor celular CXCR4. (Thesis). Universitat Ramon Llull. Retrieved from http://hdl.handle.net/10803/312147

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Planesas Galvez, Jesús M. “Estudio y cribado virtual de compuestos químicos antivirales (VIH). Estudio de la modulación alostérica de agonistas y antagonistas del receptor celular CXCR4.” 2015. Thesis, Universitat Ramon Llull. Accessed January 23, 2021. http://hdl.handle.net/10803/312147.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Planesas Galvez, Jesús M. “Estudio y cribado virtual de compuestos químicos antivirales (VIH). Estudio de la modulación alostérica de agonistas y antagonistas del receptor celular CXCR4.” 2015. Web. 23 Jan 2021.

Vancouver:

Planesas Galvez JM. Estudio y cribado virtual de compuestos químicos antivirales (VIH). Estudio de la modulación alostérica de agonistas y antagonistas del receptor celular CXCR4. [Internet] [Thesis]. Universitat Ramon Llull; 2015. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10803/312147.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Planesas Galvez JM. Estudio y cribado virtual de compuestos químicos antivirales (VIH). Estudio de la modulación alostérica de agonistas y antagonistas del receptor celular CXCR4. [Thesis]. Universitat Ramon Llull; 2015. Available from: http://hdl.handle.net/10803/312147

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

14. Barelier, Sarah. Probing protein-small molecule interactions by Nuclear Magnetic Resonance : towards a better understanding of the Fragment-Based Drug Design methodology : Étude d’interactions protéines-petites molécules par Résonance Magnétique Nucléaire : application de la méthode des fragments à la conception d’inhibiteurs de protéine.

Degree: Docteur es, Chimie, 2010, Université Claude Bernard – Lyon I

URL: http://www.theses.fr/2010LYO10222

► La méthode de conception de médicaments à partir de molécules « fragments » (connue sous le nom de « Fragment-Based Drug Design ») a été… (more)

▼ La méthode de conception de médicaments à partir de molécules « fragments » (connue sous le nom de « Fragment-Based Drug Design ») a été proposée au milieu des années 90, et a depuis été reconnue comme une alternative tangible aux techniques plus classiques de recherche de médicaments telles que le criblage à haut débit par exemple. La méthode des fragments consiste à cribler un petit nombre (< 10000) de composés organiques de faible poids moléculaire (< 300 Da) afin de détecter ceux qui se lient à la cible (protéine ou acides nucléiques). Du fait de leur faible complexité, les fragments présentent une affinité faible pour la cible, et la détection s'effectue généralement grâce à une technique biophysique (en particulier, résonance magnétique nucléaire (RMN), cristallographie aux rayons X, résonance plasmonique de surface). Les fragments « hits » sont ensuite modifiés par addition de nouvelles fonctions chimiques, ou par liaison de deux fragments, afin d'élaborer, étape par étape, une molécule capable d'établir des interactions plus nombreuses avec la cible, et d'améliorer ainsi l'affinité. Comparée aux méthodes classiques de criblage haut débit, la méthode des fragments offre divers avantages, notamment une meilleure exploration de l'espace chimique, une meilleure efficacité de liaison des molécules « hits », et une plus grande facilité d'optimisation des hits en molécules plus affines. Dans le cadre de ce projet de thèse, plusieurs aspects de la méthode des fragments ont été abordés : dans une première partie, nous étudions un cas concret d'application de la méthode des fragments à la recherche d'un inhibiteur de la peroxiredoxine 5 humaine, en utilisant la RMN comme outil de criblage des fragments ainsi que comme outil d'étude des interactions protéine-fragment. La découverte d'un inhibiteur de cette enzyme représente une avancée importante, qui devrait permettre de mieux comprendre son fonctionnement. Les autres parties de ce projet de thèse abordent des aspects plus méthodologiques de la méthode des fragments : les fragments conservent-ils leur site de liaison, leur efficacité de liaison et leur mode d'interaction au cours de leur élaboration en inhibiteur ? Les fragments peuvent-ils être spécifiques d'une protéine ? D'un site de liaison particulier ? Ces questions, rarement traitées, sont pourtant essentielles à la compréhension du comportement des molécules fragments, et sont abordées d'une part en défragmentant plusieurs inhibiteurs de la protéine Bcl-xL et en étudiant par RMN le comportement de ces fragments vis-à-vis de la protéine en termes d'affinité et de site de liaison, d'autre part en réalisant le criblage par RMN d'une série de fragments sur cinq protéines différentes (peroxiredoxine 5 humaine, sérum albumine humaine et trois protéines homologues de la famille Bcl-2). De manière générale, ce projet de thèse vise à étudier des aspects peu abordés de la méthode des fragments et à proposer des pistes permettant de mieux comprendre le comportement des fragments vis-à-vis de leur cible, au cours du… Advisors/Committee Members: Krimm, Isabelle (thesis director).

Subjects/Keywords: Conception de médicaments à partir de molécules « fragments »; Résonance Magnétique Nucléaire; Interactions Protéine-Ligand; Fragment-Based Drug Design; Nuclear Magnetic Resonance; Protein-Ligand Interactions; 572.6

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Barelier, S. (2010). Probing protein-small molecule interactions by Nuclear Magnetic Resonance : towards a better understanding of the Fragment-Based Drug Design methodology : Étude d’interactions protéines-petites molécules par Résonance Magnétique Nucléaire : application de la méthode des fragments à la conception d’inhibiteurs de protéine. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2010LYO10222

Chicago Manual of Style (16^th Edition):

Barelier, Sarah. “Probing protein-small molecule interactions by Nuclear Magnetic Resonance : towards a better understanding of the Fragment-Based Drug Design methodology : Étude d’interactions protéines-petites molécules par Résonance Magnétique Nucléaire : application de la méthode des fragments à la conception d’inhibiteurs de protéine.” 2010. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed January 23, 2021. http://www.theses.fr/2010LYO10222.

MLA Handbook (7^th Edition):

Barelier, Sarah. “Probing protein-small molecule interactions by Nuclear Magnetic Resonance : towards a better understanding of the Fragment-Based Drug Design methodology : Étude d’interactions protéines-petites molécules par Résonance Magnétique Nucléaire : application de la méthode des fragments à la conception d’inhibiteurs de protéine.” 2010. Web. 23 Jan 2021.

Vancouver:

Barelier S. Probing protein-small molecule interactions by Nuclear Magnetic Resonance : towards a better understanding of the Fragment-Based Drug Design methodology : Étude d’interactions protéines-petites molécules par Résonance Magnétique Nucléaire : application de la méthode des fragments à la conception d’inhibiteurs de protéine. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2010. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2010LYO10222.

Council of Science Editors:

Barelier S. Probing protein-small molecule interactions by Nuclear Magnetic Resonance : towards a better understanding of the Fragment-Based Drug Design methodology : Étude d’interactions protéines-petites molécules par Résonance Magnétique Nucléaire : application de la méthode des fragments à la conception d’inhibiteurs de protéine. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2010. Available from: http://www.theses.fr/2010LYO10222

Texas A&M University

15. Quinlan, Robert Jason. An investigation into the role of protein-ligand interactions on obligate and transient protein-protein interactions.

Degree: PhD, Biochemistry, 2005, Texas A&M University

URL: http://hdl.handle.net/1969.1/1430

► Protein-ligand and protein-protein interactions are critical to cellular function. Most cellular metabolic and signal tranduction pathways are influenced by these interactions, consequently molecular level understanding… (more)

▼ Protein-ligand and protein-protein interactions are critical to cellular function. Most cellular metabolic and signal tranduction pathways are influenced by these interactions, consequently molecular level understanding of these associations is an important area of biochemical research. We have examined the thermodynamics of several protein-protein associations and the protein-ligand interactions that mediate them. Using Fluorescence Correlation Spectroscopy, we have examined the putative interaction between pig heart malate dehydrogenase (MDH) and citrate synthase (CTS). We demonstrate a specific, low-affinity interaction between these enzymes. The association is highly polyethylene glycol (PEG)-dependent, and at high concentrations of NaCl or PEG, non-specific aggregates are formed. We demonstrate that oxaloacetate, the intermediate common to both CTS and MDH, induces the association at concentrations below the Km of CTS, suggesting that the open conformation of CTS is involved in the association. Using several biophysical techniques, we have examined the subunit associations of B. stearothermophilus phosphofructokinase (PFK). We demonstrate that the inhibitor bound conformation of the enzyme has reduced subunit affinity. The kinetics and thermodynamics of the phosphoenolpyrvuate (PEP)-induced dissociation of PFK have been quantified. Binding substrate, fructose-6-phosphate (F6P), stabilizes the enzyme to inhibitor-induced dissociation by 132-fold. These data suggest that subunit associations may play a role in the allosteric inhibition of PFK by PEP. The thermodynamics of the protein-ligand associations and allosteric inhibition of E. coli phosphofructokinase have been examined using intrinsic fluorescence and hydrostatic pressure. Both ligand-binding affinity and PEP inhibition are diminished by pressure, whereas substrate-binding affinity for inhibitor-bound enzyme is pressure-insensitive. Larger entropic than enthalpic changes with pressure lead to the overall reduction in free energies. Using a fluorescence-based assay, we have developed a series of baroresistant buffer mixtures. By combining a buffer with acid dissociation of negative volume with a buffer of positive volume, a pressure-resistant mixture is produced. Alteration of the molar ratio of the two component buffers yields mixtures that are pressure-insensitive at pH values around neutrality. Advisors/Committee Members: Reinhart, Gregory D. (advisor), Johnson, Arthur E. (committee member), Hu, James C. (committee member), Cremer, Paul S. (committee member).

Subjects/Keywords: protein-protein interactions; protein-ligand interactions; hydrostatic pressure; allosteric regulation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Quinlan, R. J. (2005). An investigation into the role of protein-ligand interactions on obligate and transient protein-protein interactions. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/1430

Chicago Manual of Style (16^th Edition):

Quinlan, Robert Jason. “An investigation into the role of protein-ligand interactions on obligate and transient protein-protein interactions.” 2005. Doctoral Dissertation, Texas A&M University. Accessed January 23, 2021. http://hdl.handle.net/1969.1/1430.

MLA Handbook (7^th Edition):

Quinlan, Robert Jason. “An investigation into the role of protein-ligand interactions on obligate and transient protein-protein interactions.” 2005. Web. 23 Jan 2021.

Vancouver:

Quinlan RJ. An investigation into the role of protein-ligand interactions on obligate and transient protein-protein interactions. [Internet] [Doctoral dissertation]. Texas A&M University; 2005. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1969.1/1430.

Council of Science Editors:

Quinlan RJ. An investigation into the role of protein-ligand interactions on obligate and transient protein-protein interactions. [Doctoral Dissertation]. Texas A&M University; 2005. Available from: http://hdl.handle.net/1969.1/1430

Indian Institute of Science

16. Anand, Praveen. Large-Scale Structural Analysis of Protein-ligand Interactions : Exploring New Paradigms in Anti-Tubercular Drug Discovery.

Degree: PhD, Faculty of Science, 2018, Indian Institute of Science

URL: http://etd.iisc.ac.in/handle/2005/3951

► BIOLOGICAL processes are governed through specific interactions of macromolecules. The three-dimensional structural information of the macromolecules is necessary to understand the basis of molecular recognition.… (more)

▼ BIOLOGICAL processes are governed through specific interactions of macromolecules. The three-dimensional structural information of the macromolecules is necessary to understand the basis of molecular recognition. A large number of protein structures have been determined at a high resolution using various experimental techniques such as X-ray crystallography, NMR, electron microscopy and made publicly available through the Protein Data Bank. In the recent years, comprehending function by studying a large number of related proteins is proving to be very fruitful for understanding their biological role and gaining mechanistic insights into molecular recognition. Availability of large-scale structural data has indeed made this task of predicting the protein function from three-dimensional structure, feasible. Structural bioinformatics, a branch of bioinformatics, has evolved into a separate discipline to rationalize and classify the information present in three-dimensional structures and derive meaningful biological insights. This has provided a better understanding of biological processes at a higher resolution in several cases. Most of the structural bioinformatics approaches so far, have focused on fold-level analysis of proteins and their relationship to sequences. It has long been recognized that sequence-fold or fold-function relationships are highly complex. Information on one aspect cannot be readily extrapolated to the other. To a significant extent, this can be overcome by understanding similarities in proteins by comparing their binding site structures. In this thesis, the primary focus is on analyzing the small-molecule ligand binding sites in protein structures, as most of the biological processes ranging from enzyme catalysis to complex signaling cascades are mediated through protein-ligand interactions. Moreover, given that the precise geometry and the chemical properties of the residues at the ligand binding sites dictate the molecular recognition capabilities, focusing on these sites at the structural level, is likely to yield more direct insights on protein function. The study of binding sites at the structural level poses several problems mainly because the residues at the site may be sequentially discontinuous but spatially proximal. Further, the order of the binding site residues in primary sequence, in most of cases has no significance for ligand binding. Compounding these difficulties are additional factors such as, non-uniform contribution to binding from different residues, and size-variations in binding sites even across closely related proteins. As a result, methods available to study ligand-binding sites in proteins, especially on a large-scale are limited, warranting exploration of new approaches. In the present work, new methods and tools have been developed to address some of these challenges in binding site analysis. First, a novel tool for site-based function annotation of protein structures, called PocketAnnotate was developed ( http://proline.biochem.iisc.ernet. in/pocketannotate/).… Advisors/Committee Members: Chandra, Nagasuma (advisor).

Subjects/Keywords: Protein-ligand Interactions; Anti-tubercular Drug Discovery; Protein Structure; Mycobacterium tuberculosis; Protein–ligand Complex Proteome; PDB Pocketome; Mycobacterium tuberculosis FtsZ; Helicobacter pylori DprA; Binding Site Analyses; PocketAnnotate; Protein-Ligand Interaction Clusters (PLIC); Mycobacterium tuberculosis Pocketome; Biochemistry

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APA (6^th Edition):

Anand, P. (2018). Large-Scale Structural Analysis of Protein-ligand Interactions : Exploring New Paradigms in Anti-Tubercular Drug Discovery. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/3951

Chicago Manual of Style (16^th Edition):

Anand, Praveen. “Large-Scale Structural Analysis of Protein-ligand Interactions : Exploring New Paradigms in Anti-Tubercular Drug Discovery.” 2018. Doctoral Dissertation, Indian Institute of Science. Accessed January 23, 2021. http://etd.iisc.ac.in/handle/2005/3951.

MLA Handbook (7^th Edition):

Anand, Praveen. “Large-Scale Structural Analysis of Protein-ligand Interactions : Exploring New Paradigms in Anti-Tubercular Drug Discovery.” 2018. Web. 23 Jan 2021.

Vancouver:

Anand P. Large-Scale Structural Analysis of Protein-ligand Interactions : Exploring New Paradigms in Anti-Tubercular Drug Discovery. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2018. [cited 2021 Jan 23]. Available from: http://etd.iisc.ac.in/handle/2005/3951.

Council of Science Editors:

Anand P. Large-Scale Structural Analysis of Protein-ligand Interactions : Exploring New Paradigms in Anti-Tubercular Drug Discovery. [Doctoral Dissertation]. Indian Institute of Science; 2018. Available from: http://etd.iisc.ac.in/handle/2005/3951

Indian Institute of Science

17. Ganguly, Abantika. Probing Macromolecular Reactions At Reduced Dimensionality : Mapping Of Sequence Specific And Non-Specific Protein-Ligand lnteractions.

Degree: PhD, Faculty of Science, 2015, Indian Institute of Science

URL: http://etd.iisc.ac.in/handle/2005/2478

► During the past decade the effects of macromolecular crowding on reaction pathways is gaining in prominence. The stress is to move out of the realms… (more)

▼ During the past decade the effects of macromolecular crowding on reaction pathways is gaining in prominence. The stress is to move out of the realms of ideal solution studies and make conceptual modifications that consider non-ideality as a variable in our calculations. In recent years it has been shown that molecular crowding exerts significant effects on all in vivo processes, from DNA conformational changes, protein folding to DNA-protein interactions, enzyme pathways and signalling pathways. Both thermodynamic as well as kinetic parameters vary by orders of magnitude in uncrowded buffer system as compared to those in the crowded cellular milieu. Ignoring these differences will restrict our knowledge of biology to a “model system” with few practical understandings. The recent expansion of the genome database has stimulated a study on numerous previously unknown proteins. This has whetted our thirst to model the cellular determinants in a more comprehensive manner. Intracellular extract would have been the ideal solution to re-create the cellular environment. However, studies conducted in this solution will be contaminated by interference with other biologically active molecule and relevant statistical data cannot be extracted out from it. Recent advances in methodologies to mimic the cellular crowding include use of inert macromolecules to reduce the volume occupancy of target molecules and the use of immobilization techniques to increase the surface density of molecules in a small volumetric region. The use of crowding agents often results in non-specific interaction and side-reactions like aggregation of the target molecules with the crowding agents themselves. Immobilization of one of the interacting partners reduces the probability of aggregation and precipitation of bio-macromolecules by restricting their degrees of freedom. Covalent linkage of molecules on solid support is used extensively in research for creating a homogeneous surface of bound molecules which can be interrogated for their reactivity. However, when it comes to biomolecules, direct immobilization on solid support or use of organic linkers often results in denaturation. The use of bio-affinity immobilization techniques can help us overcome this problem. Since mild conditions are needed to regenerate such a surface, it finds universal applicability as bio-memory chips. This thesis focuses on our attempts to design a physiologically viable immobilization technique for following rotein-protein/protein-DNA interactions. The work explores the mechanism for biological interactions related to transcription process in E. coli. Chapter 1 deals with the literary survey of the importance and effects of molecular crowding on biological reactions. It gives a brief history of the efforts been made so far by experimentalists, to mimic macromolecular crowding and the methods applied. The chapter tries to project an all-round perspective of the pros and cons of different immobilization techniques as a means to achieve a high surface density of molecules and… Advisors/Committee Members: Chatterji, Dipankar (advisor).

Subjects/Keywords: Molecular Crowding; Protein-Ligand Interactions; RNA Polymerase (RNAP); DNA Binding Protein; Mimic Molecular Crowding; Mycobacterium DNA Binding Protein; Bio-Macromolecules; Protein-Protein Interactions; Protein-DNA Interactions; Macromolecular Crowding; RNA Polymerase Molecule; Biochemistry

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ganguly, A. (2015). Probing Macromolecular Reactions At Reduced Dimensionality : Mapping Of Sequence Specific And Non-Specific Protein-Ligand lnteractions. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/2478

Chicago Manual of Style (16^th Edition):

Ganguly, Abantika. “Probing Macromolecular Reactions At Reduced Dimensionality : Mapping Of Sequence Specific And Non-Specific Protein-Ligand lnteractions.” 2015. Doctoral Dissertation, Indian Institute of Science. Accessed January 23, 2021. http://etd.iisc.ac.in/handle/2005/2478.

MLA Handbook (7^th Edition):

Ganguly, Abantika. “Probing Macromolecular Reactions At Reduced Dimensionality : Mapping Of Sequence Specific And Non-Specific Protein-Ligand lnteractions.” 2015. Web. 23 Jan 2021.

Vancouver:

Ganguly A. Probing Macromolecular Reactions At Reduced Dimensionality : Mapping Of Sequence Specific And Non-Specific Protein-Ligand lnteractions. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2015. [cited 2021 Jan 23]. Available from: http://etd.iisc.ac.in/handle/2005/2478.

Council of Science Editors:

Ganguly A. Probing Macromolecular Reactions At Reduced Dimensionality : Mapping Of Sequence Specific And Non-Specific Protein-Ligand lnteractions. [Doctoral Dissertation]. Indian Institute of Science; 2015. Available from: http://etd.iisc.ac.in/handle/2005/2478

University of Saskatchewan

18. Krasniqi, Besnik. Nanopore Sensing Of Peptides And Proteins.

Degree: 2013, University of Saskatchewan

URL: http://hdl.handle.net/10388/ETD-2013-11-1280

► In recent years the application of single-molecule techniques to probe biomolecules and intermolecular interactions at single-molecule resolution has expanded rapidly. Here, I investigate a series… (more)

▼ In recent years the application of single-molecule techniques to probe biomolecules and intermolecular interactions at single-molecule resolution has expanded rapidly. Here, I investigate a series of peptides and proteins in an attempt to gain a better understanding of nanopore sensing as a single-molecule technique. The analysis of retro, inversed, and retro-inversed isomers of glucagon and α-helical Fmoc-D2A10K2 peptide showed that nanopore sensing utilizing a wild-type α-hemolysin pore can distinguish between all four isomers while circular dichroism can only distinguish between chiral isomers, but not between directional isomers. The investigation of a series of proteins of different chemical and physical properties revealed important information about nanopore analysis of proteins. Contrary to some reports in the literature, all proteins analysed here induced large blockade events. The frequency of total events and the proportion of large blockade events were significantly reduced in tris(hydroxymethyl)aminomethane or 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid buffers and were only restored by the addition of ethylenediaminetetraacetic acid or the use of phosphate buffer, both of which can sequester metal ions. Furthermore, the results obtained with the proteins in the presence of ligands demonstrated that transient or partial unfolding of proteins can be detected by nanopore analysis confirming the usefulness of this technique for conformational studies or for protein/ligand interactions. Interestingly, while the blockade current histograms were different for each protein there was no obvious correlation between the properties of the proteins and the blockade current histograms. In an attempt to identify whether the large blockade events were translocation or intercalation, both an indirect and a direct approach were taken. The indirect approach which relies on the effect of voltage on the interaction of the molecule with the pore provided no conclusive answer to the question of protein translocation through the α-hemolysin pore. In contrast, the direct approach in which ribonuclease A is added to the cis side of the pore and then the trans side is tested for enzyme activity showed that ribonuclease A doesn't translocate through the α-hemolysin pore. Advisors/Committee Members: Lee, Jeremy S., Moore, Stanley, Howard, Peter, Napper, Scott.

Subjects/Keywords: nanopore; nanopore sensing; solid-state pores; alpha-hemolysin; isomers; zeta potential; metal ion binding; protein ligand interactions; Ribonuclease A

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APA (6^th Edition):

Krasniqi, B. (2013). Nanopore Sensing Of Peptides And Proteins. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/ETD-2013-11-1280

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Krasniqi, Besnik. “Nanopore Sensing Of Peptides And Proteins.” 2013. Thesis, University of Saskatchewan. Accessed January 23, 2021. http://hdl.handle.net/10388/ETD-2013-11-1280.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Krasniqi, Besnik. “Nanopore Sensing Of Peptides And Proteins.” 2013. Web. 23 Jan 2021.

Vancouver:

Krasniqi B. Nanopore Sensing Of Peptides And Proteins. [Internet] [Thesis]. University of Saskatchewan; 2013. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10388/ETD-2013-11-1280.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Krasniqi B. Nanopore Sensing Of Peptides And Proteins. [Thesis]. University of Saskatchewan; 2013. Available from: http://hdl.handle.net/10388/ETD-2013-11-1280

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

19. I. Guzzetti. INTEGRIN AND CADHERIN LIGANDS: INTERACTION STUDIES BY COMPUTATIONAL METHODS AND BIOAFFINITY NMR ON INTACT CELLS.

Degree: 2014, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/243616

► On a molecular level protein – ligand interactions are central to a number of biological processes, but their investigation is inherently difficult due to several… (more)

▼ On a molecular level protein – ligand interactions are central to a number of biological processes, but their investigation is inherently difficult due to several problems, especially for membrane proteins. The study of this type of interactions poses a whole set of challenges, including the characterization of the dynamic behaviour and of the conformational properties of the ligands in complex with the target macromolecules. A variety of biophysical methods have been developed to study protein – ligand interactions and several NMR spectroscopic techniques have emerged as powerful methods to identify and characterize the binding of ligands with receptor proteins. Ligand-based methods do not require labeled protein, since only the ligand NMR signals are detected and only a small amount of protein is required. These techniques are particularly useful in the medium–low affinity range and, therefore they have been adopted to detect ligand interactions in various systems. Among the ligand-based NMR techniques, Saturation Transfer Difference (STD) and transferred-NOE focus on the NMR signals of the ligand and utilize NOE effects between protein and ligand. They are used for: i) the definition of the bioactive conformation of the ligand in the bound state (tr-NOESY), ii) the identification and characterization of the binding mode of the ligand to the receptor with epitope mapping of the ligand itself (STD). The use of the technique is limited to molecules that exhibit a dissociation constant Kd between 10-3 M and 10-7 M. During my PhD, I had the highly qualifying opportunity to grasp these new potent NMR methods, and to apply them for assessing the interactions of cell surface proteins with peptidomimetics. Since membrane proteins, such as integrins, change their conformation if extracted from their environment, it is clear the importance of working in the biophysical neighbourhood of the membrane itself and not in an isotropic extracellular medium. For this reason, when appropriate to the project, I have carried out NMR experiments using intact cells overexpressing the proteins of interest. Specifically, two main topics have been addressed: 1. The first and second year of my PhD have been mainly focused on the conformational study of peptidomimetic integrin ligands and on the investigation of their interaction with platelets and cancer cell overexpressing integrins on their membrane. This study has been developed within the framework of a PRIN project (MIUR-PRIN project 2010NRREPL “Synthesis and Biomedical Applications of Tumor-Targeting Peptidomimetics”) in collaboration with the research groups of Proff. Gennari and Piarulli (University of Insubria) as regards the synthetic activities and with the group of Dr. Belvisi as regards the computational and design studies. 2. The second part of my PhD was mainly focused on cadherins, a class of cell adhesion proteins that promote homophilic interactions. This work is at an early stage and has been developed within the framework of a FIRB project coordinated by Dr. Civera… Advisors/Committee Members: tutor: D. Potenza, coordinatore: E. Licandro, POTENZA, DONATELLA, LICANDRO, EMANUELA.

Subjects/Keywords: STD-NMR; ligand - protein interactions; tr-NOESY; integrins; cadherins; peptidomimetic ligands; RGD ligands; Settore CHIM/06 - Chimica Organica

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APA (6^th Edition):

Guzzetti, I. (2014). INTEGRIN AND CADHERIN LIGANDS: INTERACTION STUDIES BY COMPUTATIONAL METHODS AND BIOAFFINITY NMR ON INTACT CELLS. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/243616

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Guzzetti, I.. “INTEGRIN AND CADHERIN LIGANDS: INTERACTION STUDIES BY COMPUTATIONAL METHODS AND BIOAFFINITY NMR ON INTACT CELLS.” 2014. Thesis, Università degli Studi di Milano. Accessed January 23, 2021. http://hdl.handle.net/2434/243616.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Guzzetti, I.. “INTEGRIN AND CADHERIN LIGANDS: INTERACTION STUDIES BY COMPUTATIONAL METHODS AND BIOAFFINITY NMR ON INTACT CELLS.” 2014. Web. 23 Jan 2021.

Vancouver:

Guzzetti I. INTEGRIN AND CADHERIN LIGANDS: INTERACTION STUDIES BY COMPUTATIONAL METHODS AND BIOAFFINITY NMR ON INTACT CELLS. [Internet] [Thesis]. Università degli Studi di Milano; 2014. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/2434/243616.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Guzzetti I. INTEGRIN AND CADHERIN LIGANDS: INTERACTION STUDIES BY COMPUTATIONAL METHODS AND BIOAFFINITY NMR ON INTACT CELLS. [Thesis]. Università degli Studi di Milano; 2014. Available from: http://hdl.handle.net/2434/243616

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Washington State University

20. [No author]. Effects of glucocorticoid receptor binding on base excision repair at deoxyuridine in the glucocorticoid response element .

Degree: 2006, Washington State University

URL: http://hdl.handle.net/2376/540

Subjects/Keywords: Glucocorticoids – Receptors.; Protein binding.; DNA-ligand interactions.

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APA (6^th Edition):

author], [. (2006). Effects of glucocorticoid receptor binding on base excision repair at deoxyuridine in the glucocorticoid response element . (Thesis). Washington State University. Retrieved from http://hdl.handle.net/2376/540

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

author], [No. “Effects of glucocorticoid receptor binding on base excision repair at deoxyuridine in the glucocorticoid response element .” 2006. Thesis, Washington State University. Accessed January 23, 2021. http://hdl.handle.net/2376/540.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

author], [No. “Effects of glucocorticoid receptor binding on base excision repair at deoxyuridine in the glucocorticoid response element .” 2006. Web. 23 Jan 2021.

Vancouver:

author] [. Effects of glucocorticoid receptor binding on base excision repair at deoxyuridine in the glucocorticoid response element . [Internet] [Thesis]. Washington State University; 2006. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/2376/540.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

author] [. Effects of glucocorticoid receptor binding on base excision repair at deoxyuridine in the glucocorticoid response element . [Thesis]. Washington State University; 2006. Available from: http://hdl.handle.net/2376/540

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

21. Malard, Florian. Structural and dynamic studies of TCTP protein : deciphering a complex interaction network involved in tumor reversion : Etude structurale et dynamique de la protéine TCTP : vers la caractérisation d’un réseau d’interaction complexe dans la réversion tumorale.

Degree: Docteur es, Biochimie et biologie structurale, 2019, Université Paris-Saclay (ComUE)

URL: http://www.theses.fr/2019SACLS540

►

TCTP est une petite protéine globulaire (20~kDa) qui interagit avec de nombreux partenaires et qui est impliquée dans diverses fonctions cellulaires et physiologiques, avec un… (more)

▼

TCTP est une petite protéine globulaire (20~kDa) qui interagit avec de nombreux partenaires et qui est impliquée dans diverses fonctions cellulaires et physiologiques, avec un rôle bien documenté dans la réversion tumorale qui est un phénomène rare et spontané où une cellule cancereuse perd tout ou partie de son phénotype malin et retrouve des caractéristiques associées aux cellules bénignes telles que la sensibilité à l'apoptose. Dans les cellules cancéreuses, TCTP inhibe la dégradation de MDM2, diminuant ainsi les niveaux de p53 et favorisant le maintien et la progression du cancer. TCTP contient également un motif BH3-like connu pour réguler les membres de la famille Bcl-2 et elle interagit directement avec Bcl-xL et Mcl-1 pour renforcer leurs propriétés anti-apoptotiques. Dans la structure TCTP, le motif BH3-like n'est pas facilement accessible pour une interaction avec un partenaire. Conformément à son importance dans le maintien de la tumeur, TCTP est une cible pharmacologique validée dans le traitement du cancer et fait l’objet d’essais cliniques en cours avec une molécule d'abord connue comme anti-depresseur, la sertraline. Cependant, on en sait peu sur la structure de TCTP en complexe avec ses partenaires, ce qui entrave le développement de médicaments et ne permet pas de comprendre comment TCTP peut s'adapter à une telle variété de partenaires. Ainsi, nous avons étudié le mécanisme moléculaire par lequel TCTP s'associe à des protéines et à des ligands en utilisant diverses méthodes biophysiques (RMN, SAXS, CD, SEC, DSF...). Nous avons démontré que la protéine TCTP se lie à Bcl-xL et à Mcl-1 dans le sillon de liaison des motifs BH3. Dans les complexes, la région BH3-like est engagée dans l'interface intermoléculaire et la structure centrale de TCTP est déstabilisée dans un état de globule fondu (molten-globule). Nous avons en outre montré que seule une forme mineure pré-existante de TCTP, à savoir TCTP*, est compétente pour les interactions avec les partenaires Bcl-xL et Mcl-1. Dans TCTP*, la région BH3-like est détachée du domaine structuré et elle est accessible aux protéines Bcl-xL/Mcl-1 tandis qu'on retrouve un état globule fondu dans la partie globulaire de TCTP*. Nous avons également collecté des données d'interaction préliminaires entre TCTP et la sertraline, des ARN, la protéine YB-1 se liant à l'ARN et le domaine N-terminal de MDM2. Enfin, nous avons caractérisé TCTP phosphorylé (pTCTP) au résidu S46 en utilisant la Plk-1 car cette modification a un impact sur les interactions et est un marqueur de l'aggressivité tumorale. En résumé, ces travaux ont établi la versatilité de TCTP en terme de structure et ont montré que cette versatilité est indispensable pour exercer ses fonctions cellulaires. En conséquence, ceci devrait être pris en compte dans les stratégies de développement de nouvelles molécules thérapeutiques ciblant TCTP.

TCTP is a small (20~kDa) globular protein that interacts with many partners with consequences in various cellular and physiological functions, with well-documented roles…

Advisors/Committee Members: Lescop, Ewen (thesis director).

Subjects/Keywords: Réversion tumorale; Résonance magnétique nucléaire; Interactions protéine-Ligands; Biologie structurale; Tumor reversion; Nuclear Magnetic Resonance; Protein-Ligand interaction; Structural biology

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APA (6^th Edition):

Malard, F. (2019). Structural and dynamic studies of TCTP protein : deciphering a complex interaction network involved in tumor reversion : Etude structurale et dynamique de la protéine TCTP : vers la caractérisation d’un réseau d’interaction complexe dans la réversion tumorale. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2019SACLS540

Chicago Manual of Style (16^th Edition):

Malard, Florian. “Structural and dynamic studies of TCTP protein : deciphering a complex interaction network involved in tumor reversion : Etude structurale et dynamique de la protéine TCTP : vers la caractérisation d’un réseau d’interaction complexe dans la réversion tumorale.” 2019. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed January 23, 2021. http://www.theses.fr/2019SACLS540.

MLA Handbook (7^th Edition):

Malard, Florian. “Structural and dynamic studies of TCTP protein : deciphering a complex interaction network involved in tumor reversion : Etude structurale et dynamique de la protéine TCTP : vers la caractérisation d’un réseau d’interaction complexe dans la réversion tumorale.” 2019. Web. 23 Jan 2021.

Vancouver:

Malard F. Structural and dynamic studies of TCTP protein : deciphering a complex interaction network involved in tumor reversion : Etude structurale et dynamique de la protéine TCTP : vers la caractérisation d’un réseau d’interaction complexe dans la réversion tumorale. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2019. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2019SACLS540.

Council of Science Editors:

Malard F. Structural and dynamic studies of TCTP protein : deciphering a complex interaction network involved in tumor reversion : Etude structurale et dynamique de la protéine TCTP : vers la caractérisation d’un réseau d’interaction complexe dans la réversion tumorale. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2019. Available from: http://www.theses.fr/2019SACLS540

Univerzitet u Beogradu

22. Mihailović, Jelena, 1984-, 59420681. Proteomika posttranslacionih i hemijskih modifikacija proteina i interakcije proteina od značaja u alergiji na hranu.

Degree: Hemijski fakultet, 2020, Univerzitet u Beogradu

URL: https://fedorabg.bg.ac.rs/fedora/get/o:22858/bdef:Content/get

►

Hemija - Biohemija / Chemisty - Biochemistry

Alergija na hranu je reakcija preosetljivosti imunskog sistema na hranu koja dovodi do stvaranja IgE antitela. Ne postoji… (more)

Subjects/Keywords: Food allergy; food allergens; peanut; red meat; α-Gal; EGCG; posttranslational modifications; chemical modifications; protein-ligand interactions; proteomics

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APA (6^th Edition):

Mihailović, Jelena, 1984-, 5. (2020). Proteomika posttranslacionih i hemijskih modifikacija proteina i interakcije proteina od značaja u alergiji na hranu. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:22858/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mihailović, Jelena, 1984-, 59420681. “Proteomika posttranslacionih i hemijskih modifikacija proteina i interakcije proteina od značaja u alergiji na hranu.” 2020. Thesis, Univerzitet u Beogradu. Accessed January 23, 2021. https://fedorabg.bg.ac.rs/fedora/get/o:22858/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mihailović, Jelena, 1984-, 59420681. “Proteomika posttranslacionih i hemijskih modifikacija proteina i interakcije proteina od značaja u alergiji na hranu.” 2020. Web. 23 Jan 2021.

Vancouver:

Mihailović, Jelena, 1984- 5. Proteomika posttranslacionih i hemijskih modifikacija proteina i interakcije proteina od značaja u alergiji na hranu. [Internet] [Thesis]. Univerzitet u Beogradu; 2020. [cited 2021 Jan 23]. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:22858/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mihailović, Jelena, 1984- 5. Proteomika posttranslacionih i hemijskih modifikacija proteina i interakcije proteina od značaja u alergiji na hranu. [Thesis]. Univerzitet u Beogradu; 2020. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:22858/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Duke University

23. Xu, Ying. Development and Applications of Chemical Labeling Protocols for Protein-Ligand Binding Analysis Using Bottom-Up Proteomics .

Degree: 2011, Duke University

URL: http://hdl.handle.net/10161/5640

► Proteins fold into well-defined three-dimensional structures to carry out their biological functions which involve non-covalent interactions with other cellular molecules. Knowledge about the thermodynamic… (more)

▼ Proteins fold into well-defined three-dimensional structures to carry out their biological functions which involve non-covalent interactions with other cellular molecules. Knowledge about the thermodynamic properties of proteins and protein-ligand complexes is essential for answering fundamental biological questions and drug or biomarker discovery. Recently, chemical labeling strategies have been combined with mass spectrometry methods to generate thermodynamic information about protein folding and ligand binding interactions. The work in this thesis is focused on the development and application of two such chemical labeling protocols coupled with mass spectrometry including one termed, SUPREX (stability of unpurified proteins from rates of H/D exchange), and one termed SPROX (stability of proteins from rates of oxidation). The work described in this thesis is divided into two parts. The first part involves the application of SUPREX to the thermodynamic analysis of a protein folding chaperone, Hsp33, and its interaction with unfolded protein substrates. The second part involves the development of a new chemical labeling protocol that can be used to make protein folding and ligand binding measurements on the proteomic scale. In the first part of this work, the SUPREX technique was used to study the binding interaction between the molecular chaperone Hsp33 and four different unfolded protein substrates including citrate synthase, lactate dehydrogenase, malate dehydrogenase, and aldolase. The results of the studies, which were performed at the intact protein level, suggest that the cooperativity of the Hsp33 folding/unfolding reaction increases upon binding with denatured protein substrates. This is consistent with the burial of significant hydrophobic surface area in Hsp33 when it interacts with its substrate proteins. The SUPREX derived Kd-values for Hsp33 complexes with four different substrates were also found to be all within a range of 3-300 nM. The interaction between Hsp33 and one of its substrates, citrate synthase (CS), was characterized at a higher structural resolution by using the SUPREX technique in combination with a protease digestion protocol. Using this protocol, the thermodynamic properties for both Hsp33 and CS were evaluated at different stages of binding, including reduced Hsp33 (inactive form), oxidized Hsp33 (active form), followed by native CS and finally of Hsp33ox -CS complexes before and after reduction with DTT. The results suggest that Hsp33 binds unfolded proteins that still have a significant amount of residual higher- order structure. Structural rearrangements of the substrate protein appear to occur upon reduction of the Hsp33-substrate complexes, which may facilitate the transfer of the substrate protein to other protein folding chaperone systems. In the second part of this dissertation, a mass spectrometry-based covalent labeling protocol, which relies on the amidination rate of globally protected protein amine groups, was designed and applied to the thermodynamic… Advisors/Committee Members: Fitzgerald, Michael C (advisor).

Subjects/Keywords: Analytical Chemistry; Chaprone proteins; Chemical Labeling; Mass Spectrometry; Probing buried amine groups; Protein-ligand interactions; Thermodynamic Stability

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APA (6^th Edition):

Xu, Y. (2011). Development and Applications of Chemical Labeling Protocols for Protein-Ligand Binding Analysis Using Bottom-Up Proteomics . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/5640

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Xu, Ying. “Development and Applications of Chemical Labeling Protocols for Protein-Ligand Binding Analysis Using Bottom-Up Proteomics .” 2011. Thesis, Duke University. Accessed January 23, 2021. http://hdl.handle.net/10161/5640.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Xu, Ying. “Development and Applications of Chemical Labeling Protocols for Protein-Ligand Binding Analysis Using Bottom-Up Proteomics .” 2011. Web. 23 Jan 2021.

Vancouver:

Xu Y. Development and Applications of Chemical Labeling Protocols for Protein-Ligand Binding Analysis Using Bottom-Up Proteomics . [Internet] [Thesis]. Duke University; 2011. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10161/5640.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Xu Y. Development and Applications of Chemical Labeling Protocols for Protein-Ligand Binding Analysis Using Bottom-Up Proteomics . [Thesis]. Duke University; 2011. Available from: http://hdl.handle.net/10161/5640

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toledo

24. Mishra, Vidhi. Structural and Biochemical Studies of Protein-Ligand Interactions: Insights for Drug Development.

Degree: PhD, Chemistry, 2013, University of Toledo

URL: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1384637704

► Protein ligand interactions play a key role in the majority of all biological processes. Proteins display unique binding sites that are recognized by specific… (more)

▼ Protein ligand interactions play a key role in the majority of all biological processes. Proteins display unique binding sites that are recognized by specific ligand through distinct interactions. Characterization of these interactions provides insights that are exploitable for designing drugs. Here we study enzyme-substrate interactions in a protein encoded by Helicobacter pylori (H. pylori), which is associated with gastric and duodenal ulcers. H. pylori MTAN (HpMTAN) catalyzes the hydrolysis of N-ribosidic bonds of at least four different adenosine based substrates; S-adenosylhomocysteine (SAH), 5'-methylthioadenosine (MTA), 5'-deoxyadeosine (5'-DOA) and 6-amino-6-deoxyfutalosine. This hydrolytic activity places MTAN at the hub of at least seven fundamental metabolic pathways: the purine salvage pathway, the methionine salvage pathway, S-adenosylmethionine (SAM)-dependent methylation pathways, polyamine biosynthesis, the production of quorum sensing molecules and menaquinone biosynthesis. Campylobacter and Helicobacter are dependent on MTAN for menaquinone synthesis, an essential metabolite for bacterial viability, making MTAN an excellent target for the development of new treatments for Helicobacter infections. To structurally characterize the interactions between MTAN and its various substrates, complexes of an inactive mutant of the HpMTAN with two known substrates, 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH) were formed and crystallized. The crystal structures of mutant HpMTAN complexed with SAH and MTA were solved to 1.2 and 1.6 A respectively. The HpMTAN-SAH co-crystal structure represents the first visualization of interactions between the homocysteine moiety of SAH and the 5'-alkylthiol-binding subsite of the MTAN active site. The co-crystal structure of wild-type MTAN with products, adenine and S-ribosylhomocysteine, was determined to 1.54 A resolution. The similarities and differences in these three structures highlight features that can be exploited to design H. pylori specific drugs. Additionally, a high-throughput fluorescence polarization assay was developed and optimized that will afford the identification of new drug scaffolds that bind to the H. pylori MTAN active site. Additionally, we studied the I1 protein that is essential for the assembly of vaccinia virus. I1 is a telomere binding protein. We performed structural and biochemical characterizations to understand the mechanism of protein-DNA interaction. Finally, we studied a protein involved in the folate biosynthetic pathway for drug discovery purpose against Mycobacterium tuberculosis. Advisors/Committee Members: Ronning, Donald (Committee Chair).

Subjects/Keywords: Chemistry; Structural studies; biochemical studies; protein-ligand interactions; drug development; Helicobacter pylori; MTAN; SAH; vaccinia virus; Mycobacterium tuberculosis; folate biosynthetic pathway

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mishra, V. (2013). Structural and Biochemical Studies of Protein-Ligand Interactions: Insights for Drug Development. (Doctoral Dissertation). University of Toledo. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=toledo1384637704

Chicago Manual of Style (16^th Edition):

Mishra, Vidhi. “Structural and Biochemical Studies of Protein-Ligand Interactions: Insights for Drug Development.” 2013. Doctoral Dissertation, University of Toledo. Accessed January 23, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1384637704.

MLA Handbook (7^th Edition):

Mishra, Vidhi. “Structural and Biochemical Studies of Protein-Ligand Interactions: Insights for Drug Development.” 2013. Web. 23 Jan 2021.

Vancouver:

Mishra V. Structural and Biochemical Studies of Protein-Ligand Interactions: Insights for Drug Development. [Internet] [Doctoral dissertation]. University of Toledo; 2013. [cited 2021 Jan 23]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1384637704.

Council of Science Editors:

Mishra V. Structural and Biochemical Studies of Protein-Ligand Interactions: Insights for Drug Development. [Doctoral Dissertation]. University of Toledo; 2013. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1384637704

Indian Institute of Science

25. Bhagavat, Raghu B R. Structural Bioinformatics of Ligand Recognition in Proteins : A large-scale Analysis and Applications in Drug Discovery.

Degree: PhD, Faculty of Science, 2019, Indian Institute of Science

URL: http://etd.iisc.ac.in/handle/2005/4249

► Biological processes are governed by highly specific macromolecular interactions. Understanding the precise mechanism of ligand recognition in proteins is essential for deriving features responsible for… (more)

▼ Biological processes are governed by highly specific macromolecular interactions. Understanding the precise mechanism of ligand recognition in proteins is essential for deriving features responsible for such recognition capabilities. Although protein sequences give first-hand information about their function, their three-dimensional structures, which are the evolutionary units, convey the function better. Three-dimensional structures of many proteins determined through X-ray crystallography and/or NMR are available in the Protein Data Bank, a public repository. This resource has stimulated the development of computational techniques to read and analyse the wealth of structural data. Structural bioinformatics is an area that provides a means to transform information in the protein structures into functional insights and enable addressing a variety of questions about what defines and dictates ligand recognition. Large-scale analyses of several protein-ligand complexes have indicated that both one-to-many and many-to-one relationships of protein-folds and ligand-types are widely seen in the PDB. This means that a given ligand can be recognized by diverse proteins and a given protein can recognize different types of ligands at the same location, ligands referring to endogenous ligands, natural metabolites as well as small molecule inhibitors, and drugs. Given this, it is important to understand the determinants of recognition of a given ligand. This becomes important for applications in drug discovery that includes, lead design and lead optimization, assessment of draggability of a target, identification of off-target effects, polypharmacological targets and drug repurposing. The present work utilizes the information present at the functional sites, rationalizing many examples of ligand binding and deriving useful patterns that can be used for genome-wide function annotation and drug discovery applications. A large-scale analysis of the binding of two important classes of ligands, a sugar and nucleotides was carried out by analysing the sub-structures at their binding sites by matching, aligning and clustering. The two ligands studied are sialic acid, and nucleoside mon/di/tri phosphates (nucleotides or NTPs), for their binding to many proteins reported in the PDB. Sialic acid was found to be recognized by 170 different proteins representing 17 unique sequence families. Our approach deciphered a unified understanding of the basis of recognition of this ligand and showed six structural motifs, which contained different combinations of one or more key structural features, over a common scaffold. The site features refer to certain residues in the binding site that are seen to most frequently occur at their respective topological positions, a result that was evident upon binding site comparisons and 3-D alignment of sites in the different proteins. In the case of nucleotide ligands, 4,677 structures of protein-nucleotide complexes from PDB, belonging to 145 different structural folds and 394 sequence families were… Advisors/Committee Members: Chandra, Nagasuma (advisor), Srinivasan, N (advisor).

Subjects/Keywords: Protein-ligand Interactions; Ligand Recognition; Drug Discovery; Sialic Acid Binding Proteins; Pocketome; Nucleoside Diphosphate Kinase (NDK); Nucleotide Binding Proteins; Mycobacterial Genomes; Biotechnology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bhagavat, R. B. R. (2019). Structural Bioinformatics of Ligand Recognition in Proteins : A large-scale Analysis and Applications in Drug Discovery. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/4249

Chicago Manual of Style (16^th Edition):

Bhagavat, Raghu B R. “Structural Bioinformatics of Ligand Recognition in Proteins : A large-scale Analysis and Applications in Drug Discovery.” 2019. Doctoral Dissertation, Indian Institute of Science. Accessed January 23, 2021. http://etd.iisc.ac.in/handle/2005/4249.

MLA Handbook (7^th Edition):

Bhagavat, Raghu B R. “Structural Bioinformatics of Ligand Recognition in Proteins : A large-scale Analysis and Applications in Drug Discovery.” 2019. Web. 23 Jan 2021.

Vancouver:

Bhagavat RBR. Structural Bioinformatics of Ligand Recognition in Proteins : A large-scale Analysis and Applications in Drug Discovery. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2019. [cited 2021 Jan 23]. Available from: http://etd.iisc.ac.in/handle/2005/4249.

Council of Science Editors:

Bhagavat RBR. Structural Bioinformatics of Ligand Recognition in Proteins : A large-scale Analysis and Applications in Drug Discovery. [Doctoral Dissertation]. Indian Institute of Science; 2019. Available from: http://etd.iisc.ac.in/handle/2005/4249

McMaster University

26. Boulton, Stephen. Mapping Allosteric Sites and Pathways in Systems Unamenable to Traditional Structure Determination.

Degree: PhD, 2018, McMaster University

URL: http://hdl.handle.net/11375/23697

►

Allostery is a regulatory process whereby a perturbation by an effector at one discrete locus creates a conformational change that stimulates a functional change at… (more)

▼

Allostery is a regulatory process whereby a perturbation by an effector at one discrete locus creates a conformational change that stimulates a functional change at another. The two sites communicate through networks of interacting residues that respond in a concerted manner to the allosteric perturbation. These allosteric networks are traditionally mapped with high resolution structure determination techniques to understand the conformational changes that regulate protein function as well as its modulation by allosteric ligands and its dysfunction caused by disease-related mutations (DRMs). However, high resolution structural determination techniques, such as X-ray crystallography, cryo-electron microscopy and nuclear Overhauser effect NMR spectroscopy are not always amenable for systems plagued by poor solubility and line broadening caused by μs-ms dynamics or systems where allostery relies primarily on dynamical rather than structural changes. This dissertation discusses methodologies to map the allosteric sites and pathways for such challenging systems. The foundation of this approach is to model allosteric pathways in the context of their respective thermodynamic cycles. In chapter 2, the thermodynamic cycle of a DRM in the hyperpolarization-activated cyclic nucleotide-gated ion channel 4 (HCN4) is analyzed with respect to structure, dynamics and kinetics, revealing how the DRM remodels the free energy landscape of HCN4 and results in a loss-of-function disease phenotype. In chapter 3, the mechanism of action of an uncompetitive inhibitor for the exchange protein activated by cAMP is elucidated by characterizing its selectivity for distinct conformations within the thermodynamic cycle that are trapped using a combination of mutations and ligand analogs. In chapter 4, we discuss two new protocols for the chemical shift covariance analysis (CHESCA). The CHESCA is an approach that identifies allosteric signaling pathways by measuring concerted residue responses to a library of chemical perturbations that stabilize conformational equilibria at different positions. Overall, the approaches discussed in this dissertation are widely applicable for mapping the mechanisms of allosteric perturbations that arise from ligand binding, post-translational modifications and mutations, even in systems where traditional structure determination techniques remain challenging to implement.

Thesis

Doctor of Philosophy (PhD)

Allostery is a regulatory mechanism for proteins, which controls functional properties of one distinct site through the perturbation of another distinct, and often distant, site. The two sites are connected via a series of residues that undergo conformational changes once perturbed by the allosteric effector. Mapping these communication pathways reveals mechanisms of protein regulation, which are invaluable for developing pharmacological modulators to target these pathways or for understanding the mechanisms of disease mutations that disrupt these pathways. Allosteric pathways have been traditionally…

Advisors/Committee Members: Melacini, Giuseppe, Health Sciences.

Subjects/Keywords: Allostery; Protein Regulation; Protein-Ligand Interactions; Cell Signaling; Cyclic Nucleotides; NMR Spectroscopy; Protein Dynamics; Drug Development; Disease Mutations; Biochemistry; Ion Channels; Enzyme Inhibition

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Boulton, S. (2018). Mapping Allosteric Sites and Pathways in Systems Unamenable to Traditional Structure Determination. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/23697

Chicago Manual of Style (16^th Edition):

Boulton, Stephen. “Mapping Allosteric Sites and Pathways in Systems Unamenable to Traditional Structure Determination.” 2018. Doctoral Dissertation, McMaster University. Accessed January 23, 2021. http://hdl.handle.net/11375/23697.

MLA Handbook (7^th Edition):

Boulton, Stephen. “Mapping Allosteric Sites and Pathways in Systems Unamenable to Traditional Structure Determination.” 2018. Web. 23 Jan 2021.

Vancouver:

Boulton S. Mapping Allosteric Sites and Pathways in Systems Unamenable to Traditional Structure Determination. [Internet] [Doctoral dissertation]. McMaster University; 2018. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/11375/23697.

Council of Science Editors:

Boulton S. Mapping Allosteric Sites and Pathways in Systems Unamenable to Traditional Structure Determination. [Doctoral Dissertation]. McMaster University; 2018. Available from: http://hdl.handle.net/11375/23697

York University

27. Bao, Jiayin. Novel Kinetic Solution-Based Separation Approaches for Small Molecule Drug Discovery.

Degree: PhD, Chemistry, 2017, York University

URL: http://hdl.handle.net/10315/33488

► The modern pharmaceutical industry has achieved remarkable successes in medicinal chemistry. However, many diseases are incurable due to the difficulty of finding new drugs. De… (more)

▼ The modern pharmaceutical industry has achieved remarkable successes in medicinal chemistry. However, many diseases are incurable due to the difficulty of finding new drugs. De novo drug discovery contains two steps: the primary screening focuses on selecting protein (target) binding drug (ligand); the secondary screening concentrates on calculating kinetic binding parameters of target-ligand complex. Conventional methods for the primary screening are typically surface-based, which suffer intensely from nonspecific interactions; the existing methods for secondary screening are either affinity-based or require surface immobilization, both cannot accurately calculate kinetic binding parameters. Hence, this research focuses on the development of the solution-based kinetic platform that facilitates both primary and secondary screenings. We combined kinetic capillary electrophoresis (KCE) with DNA-encoded ligand (DEL) technology to build a solution-based platform for primary screening of ligands. KCE offers high partitioning efficiency but requires the knowledge of electrophoretic mobility of target-ligand complex, and thus, we developed a mathematical model to predict electrophoretic mobility of target-DEL complex. This model was tested by using the targets interacted with 18 artificial DELs that contain various combinations of dsDNA and ssDNA regions, together with 2 DELs manufactured by GlaxoSmithKline. The results confirmed the precision, accuracy, and ruggedness of our model. This model will facilitate the reliable use of KCE-DEL based primary screening. Next, we developed a kinetic size-exclusion chromatography-mass spectrometry (KSEC-MS) as the label-free solution-based platform for calculating kinetic binding parameters of target-ligand interactions in secondary screening. KSEC-MS employs size-exclusion chromatography to separate small molecule ligand from protein target-ligand complex without immobilization and mass spectrometry to detect small molecule without a label. The rate constants of complex formation and dissociation are calculated from the temporal ligand concentration profile. Methods of KSEC-MS have been developed by using 2 proteins with the corresponding drugs. The resulted kinetic and affinity binding parameters were validated, which confirmed the precision and accuracy of KSEC-MS. We foresee that the KSEC-MS will become a universal approach for the kinetic analysis of target-ligand interactions in secondary screening. Advisors/Committee Members: Krylov, Sergey N. (advisor).

Subjects/Keywords: Pharmaceutical sciences; Analytical chemistry; Biomolecular interactions; Protein-small molecule interactions; Drug screening; Target-ligand interactions; Label-free drug selections; Solution based-kinetic methods; KSEC-MS; KCE-MS; KCE; Mass spectrometry; Kinetic size-exclusion chromatography; DNA-encoded ligand; DEL

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bao, J. (2017). Novel Kinetic Solution-Based Separation Approaches for Small Molecule Drug Discovery. (Doctoral Dissertation). York University. Retrieved from http://hdl.handle.net/10315/33488

Chicago Manual of Style (16^th Edition):

Bao, Jiayin. “Novel Kinetic Solution-Based Separation Approaches for Small Molecule Drug Discovery.” 2017. Doctoral Dissertation, York University. Accessed January 23, 2021. http://hdl.handle.net/10315/33488.

MLA Handbook (7^th Edition):

Bao, Jiayin. “Novel Kinetic Solution-Based Separation Approaches for Small Molecule Drug Discovery.” 2017. Web. 23 Jan 2021.

Vancouver:

Bao J. Novel Kinetic Solution-Based Separation Approaches for Small Molecule Drug Discovery. [Internet] [Doctoral dissertation]. York University; 2017. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10315/33488.

Council of Science Editors:

Bao J. Novel Kinetic Solution-Based Separation Approaches for Small Molecule Drug Discovery. [Doctoral Dissertation]. York University; 2017. Available from: http://hdl.handle.net/10315/33488

28. Jurisinec, Ashley. Quadruplex stabilising Pt(II) complexes.

Degree: 2019, Western Sydney University

URL: http://hdl.handle.net/1959.7/uws:57519

► G-Quadruplex DNA (QDNA) motifs have been observed to form in various important regions of the human genome, contributing to cellular processes such as gene expression,… (more)

Subjects/Keywords: DNA-binding proteins; Thesis (M.Res.) – Western Sydney University, 2019; DNA-protein interactions; DNA-ligand interactions; transition metal complexes; synthesis; gene expression; telomere

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jurisinec, A. (2019). Quadruplex stabilising Pt(II) complexes. (Thesis). Western Sydney University. Retrieved from http://hdl.handle.net/1959.7/uws:57519

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jurisinec, Ashley. “Quadruplex stabilising Pt(II) complexes.” 2019. Thesis, Western Sydney University. Accessed January 23, 2021. http://hdl.handle.net/1959.7/uws:57519.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jurisinec, Ashley. “Quadruplex stabilising Pt(II) complexes.” 2019. Web. 23 Jan 2021.

Vancouver:

Jurisinec A. Quadruplex stabilising Pt(II) complexes. [Internet] [Thesis]. Western Sydney University; 2019. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1959.7/uws:57519.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jurisinec A. Quadruplex stabilising Pt(II) complexes. [Thesis]. Western Sydney University; 2019. Available from: http://hdl.handle.net/1959.7/uws:57519

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas Tech University

29. Baker, Cheryl H. The role of positions 99 and 127 in cAMP-mediated activation of CRP.

Degree: Chemistry, 1999, Texas Tech University

URL: http://hdl.handle.net/2346/19257

► The cycHc 3':5'-adenosine monophosphate (cAMP) receptor protein (CRP) of Escherichia coli hinds cycHc nucleotides. When complexed with cAMP, CRP binds to specific DNA sequences located… (more)

▼ The cycHc 3':5'-adenosine monophosphate (cAMP) receptor protein (CRP) of Escherichia coli hinds cycHc nucleotides. When complexed with cAMP, CRP binds to specific DNA sequences located upstream of a number of promoters leading to the formation of active transcription complexes composed of CRP, cAMP, DNA, and RNA polymerase (RNAP). Molecular dynamics (MD) simulations were performed on CRP:(cAMP)2 structure. Analysis of amino acid residue proximities to cAMP in the MD-CRP:(cAMP)2 complex confirmed that known protein/Ugand contacts were maintained during the simidation and revealed the repositioning of tyrosine at position 99 (Y99) to interact with cAMP. To determine the vahdity of the MDpredicted Y99:cAMP interaction the crp gene was mutated to replace the Y99 codon with either an alanine (A) or a phenylalanine (F) codon. The mutant genes were expressed and characterized in vivo. Cells that contained wildtype (WT), alanine (Y99A), or phenylalanine (Y99F) CRP expressed pgalactosidase only when cultured in the presence of cAMP. Those cultures that contained Y99A or Y99F CRP showed cAMP-dependent inhibition of cell growth. In vitro studies showed that purified WT, Y99A and Y99F CRP found sequentially two molecules of cAMP, exhibited negative cooperativity in cAMP binding and activated the lactose promoter (lacP)in the presence of cAMP. These data, when coupled with the characteristics of cAMPS(Rp)binding to and effect on WT CRP, are consistent with a Y99:R82:cAMP interaction observed for the CRP:(cAMP)2 complex. In addition to the Y99 studies, the DNA binding and lacP activation characteristics of mutant forms of CRP (cysteine [C], glycine [G], isoleucine [I] or serine [S] for threonine [T]) at position 127 were investigated. The results demonstrated that allosteric changes important for cAMP-mediated CRP DNA binding is differentially affected by amino acid substitution at position 127. However, cAMP-dependent interaction of CRP with RNAP observed regardless of the amino acid at position 127. This study further investigates the characteristics of these mutants with respect to lacP DNAand cAMP-binding. The results lead to the conclusion that threonine 127 plays an important role in transduction of the signal from the CRP cyclic nucleotide binding pocket that promotes proper orientation of the DNAbinding helices and only a minor, if any, role in the functional exposure of the CRP RNAP interaction domain.

Subjects/Keywords: Molecular dynamics; Deoxyribonucleic acid (DNA)-protein interactions; Deoxyribonucleic acid (DNA)-ligand interactions

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Baker, C. H. (1999). The role of positions 99 and 127 in cAMP-mediated activation of CRP. (Thesis). Texas Tech University. Retrieved from http://hdl.handle.net/2346/19257

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Baker, Cheryl H. “The role of positions 99 and 127 in cAMP-mediated activation of CRP.” 1999. Thesis, Texas Tech University. Accessed January 23, 2021. http://hdl.handle.net/2346/19257.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Baker, Cheryl H. “The role of positions 99 and 127 in cAMP-mediated activation of CRP.” 1999. Web. 23 Jan 2021.

Vancouver:

Baker CH. The role of positions 99 and 127 in cAMP-mediated activation of CRP. [Internet] [Thesis]. Texas Tech University; 1999. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/2346/19257.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Baker CH. The role of positions 99 and 127 in cAMP-mediated activation of CRP. [Thesis]. Texas Tech University; 1999. Available from: http://hdl.handle.net/2346/19257

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

30. Olivieri, Lilian. Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations.

Degree: Docteur es, Biologie informatique, 2012, La Réunion

URL: http://www.theses.fr/2012LARE0011

►

FKBP12 est une protéine ubiquitaire, principalement cytosolique, qui est au carrefour de plusieurs voies signalétiques. Son abondance naturelle dans les tissus nerveux peut être reliée… (more)

▼

FKBP12 est une protéine ubiquitaire, principalement cytosolique, qui est au carrefour de plusieurs voies signalétiques. Son abondance naturelle dans les tissus nerveux peut être reliée à son implication dans les maladies neurodégénératives telles que les maladies d'Alzheimer et de Parkinson ainsi que dans les neuropathies périphériques et diabétiques ou dans des blessures des cordons spinaux. De nombreuses études ont montré que des molécules exogènes (ligands) venant se fixer sur cette protéine permettent la régénération d'un grand nombre de connexions neuronales endommagées. Une difficulté provient cependant du fait que, pour un ligand donné, il n'existe aucune relation claire entre sa structure et sa capacité de liaison à FKBP12. Notre étude vise ainsi à rationaliser la relation entre la structure d'un ligand et son affinité pour cette protéine. Deux complexes modèles, formés entre FKBP12 et chacun des deux ligands 8 et 308, ont été utilisés. Ces deux ligands de haute affinité ont des structures différentes. Notre travail s'est appuyé sur des simulations de dynamique moléculaire pour caractériser l'état intermédiaire qui est formé transitoirement lors du processus de complexation entre la protéine et son ligand. Dans cet état particulier, l'identification des interactions naissantes entre les partenaires a permis (i) de comprendre l'implication des différentes parties du ligand dans le mécanisme de reconnaissance avec FKBP12 et (ii) de rationaliser les affinités de certains ligands apparentés.

FKBP12 is an ubiquitous, mostly cytosolic, protein found at the crossroads of several signaling pathways. Its natural abundance in the nervous tissues can be related to its implication in neurodegenerative diseases like Alzheimer's and Parkinson's as well as in peripheral neuropathies and diabetes or in injuries of the spinal cords. Several studies have demonstrated that exogenous molecules (ligands) that can bind to FKBP12 allow the regeneration of many damaged neuron connections. However, there is no clear relationship between the structure of a ligand and its ability to bind to FKBP12. Our study aims at rationalizing the relationship between the structure of a ligand and its affinity to FKBP12. Two model complexes, formed between FKBP12 and each of the two high-affinity ligands 8 and 308, were studied. These two ligands are structurally different. We used molecular dynamics simulations to characterize the intermediate state that is transiently formed during the binding process between the protein and its ligand. In this state, the analysis of the nascent interactions allowed (i) to unravel the role played by the various ligand moieties in the recognition process with FKBP12 and (ii) to rationalize the affinities of related ligands.

Advisors/Committee Members: Offmann, Bernard (thesis director), Gardebien, Fabrice (thesis director).

Subjects/Keywords: Fkbp12; État intermédiaire de complexation; Reconnaissance moléculaire; Interactions protéine-Ligand; Simulations de dynamique moléculaire; Ligand de haute affinité; Paramétrisation d’un champ de force; Calculs Hartree-Fock; Fkbp12; BÉtat intermédiaire de complexationinding intermediate state; Molecular recognition; Protein-Ligand interactions; Molecular dynamics simulations; High-Affinity ligand; Force field parameterization; Hartree-Fock calculations

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Olivieri, L. (2012). Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations. (Doctoral Dissertation). La Réunion. Retrieved from http://www.theses.fr/2012LARE0011

Chicago Manual of Style (16^th Edition):

Olivieri, Lilian. “Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations.” 2012. Doctoral Dissertation, La Réunion. Accessed January 23, 2021. http://www.theses.fr/2012LARE0011.

MLA Handbook (7^th Edition):

Olivieri, Lilian. “Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations.” 2012. Web. 23 Jan 2021.

Vancouver:

Olivieri L. Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations. [Internet] [Doctoral dissertation]. La Réunion; 2012. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2012LARE0011.

Council of Science Editors:

Olivieri L. Recherche et caractérisation par dynamique moléculaire d'états intermédiaires pour la complexation entre la protéine FKBP12 et des ligands de haute affinité : Study of building intermediate states between FKBP12 and high-affinity ligands by molecular dynamics simulations. [Doctoral Dissertation]. La Réunion; 2012. Available from: http://www.theses.fr/2012LARE0011

Open Access Theses and Dissertations