subject:(protein dynamics)

University of Notre Dame

1. John S Zintsmaster. A Network of Residues Relevant to Enzymatic Function in Pin1: A Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Approach</h1>.

Degree: Chemistry and Biochemistry, 2013, University of Notre Dame

URL: https://curate.nd.edu/show/73666397w5f

► Proteins are in constant motion and these motions impact their function. This thesis attempts to use simple perturbative techniques to track the changes in… (more)

▼ Proteins are in constant motion and these motions impact their function. This thesis attempts to use simple perturbative techniques to track the changes in dynamics upon disrupting the native state of a protein. The protein studied within this thesis is the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1). Pin1’s function has been extensively studied (Lu 1996) (Ranganathan 1997) (Zhou 1999) (Verdecia 2000) (Wintjens 2001) (Bayer 2003) (Jacobs 2003) (Mueller 2011), yet a single, all-encompassing mechanistic explanation has not been provided. The dynamics of Pin1 has been shown to be closely related to catalysis and function (Namanja 2007) (T. Peng 2007) (Namanja 2011). Thus, Pin1 is an ideal candidate for both a toy system for studying different aspects of the relation between protein dynamics and function as well as a worthwhile protein for studying its specific, practically important functional mechanism. This thesis utilizes a wide variety of experimental and computer based techniques to study the dynamics of Pin1 over timescales ranging from ps to ms. First a novel study of ligand dynamics during catalysis is presented. These NMR experiments are completed at natural isotopic abundance and monitor the μs-ms dynamics of an enzyme-substrate pair. This work represents the first ever study of ligand relaxation dispersion measurements at natural isotopic abundance (Zintsmaster 2008).Next, a brief look at the application of a Gaussian Network Model (GNM) (Bahar 1997) to monitor changes in dynamics upon mutation/deletion is presented. GNM flexibility profiles provide a quick, qualitative means for looking at changes in flexibility upon changes in 3-dimensional structure. Experimental data is compared to the GNM profiles and a good agreement between experiment and GNM is seen. This section will focus on the study of the WW domain of Pin1. Chapter 6 addresses the issue of domain-domain coupling. Pin1 is a two domain protein connected by a flexible 10 residue linker. First NMR order parameters from experiment and MD simulations are compared in an effort to scrutinize the results of both simulation and experiment. Next, the conditions with the greatest degree of agreement are used to simulate the dynamics of full length Pin1 vs. the two isolated domains, the WW domain and the PPIase domain. It is hypothesized that the difference in dynamics of these two simulations can shed light on the weak interactions contributing to domain-domain coupling in full length Pin1. Analysis of these differences dynamic changes at sites that coincide with those undergoing changes upon substrate binding. The last chapter, Chapter 7, deals with MD simulations of three Pin1 single residue mutants. The first two mutants, C113A (Winkler 2000) and T152A (Mueller 2011), have been previously shown to inactivate enzymatic activity in Pin1. Furthermore, Winkler et al. have shown that in crystal structures of Par14, a close relative of human Pin1, an extended hydrogen bonding network can be seen stretching from T152 to… Advisors/Committee Members: Steven Corcelli, Committee Member, Dan Gezelter, Committee Member, Masaru K. Kuno, Committee Member.

Subjects/Keywords: protein dynamics; pin1

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Zintsmaster, J. S. (2013). A Network of Residues Relevant to Enzymatic Function in Pin1: A Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Approach</h1>. (Thesis). University of Notre Dame. Retrieved from https://curate.nd.edu/show/73666397w5f

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):

Zintsmaster, John S. “A Network of Residues Relevant to Enzymatic Function in Pin1: A Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Approach</h1>.” 2013. Thesis, University of Notre Dame. Accessed January 17, 2021. https://curate.nd.edu/show/73666397w5f.

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

MLA Handbook (7^th Edition):

Zintsmaster, John S. “A Network of Residues Relevant to Enzymatic Function in Pin1: A Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Approach</h1>.” 2013. Web. 17 Jan 2021.

Vancouver:

Zintsmaster JS. A Network of Residues Relevant to Enzymatic Function in Pin1: A Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Approach</h1>. [Internet] [Thesis]. University of Notre Dame; 2013. [cited 2021 Jan 17]. Available from: https://curate.nd.edu/show/73666397w5f.

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

Council of Science Editors:

Zintsmaster JS. A Network of Residues Relevant to Enzymatic Function in Pin1: A Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Approach</h1>. [Thesis]. University of Notre Dame; 2013. Available from: https://curate.nd.edu/show/73666397w5f

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

2. Bolin, Eric. Characterizing rare and transient conformations of proteins using amide hydrogen exchange and thiol exchange.

Degree: Biophysics, 2018, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/1cd158xw

► The dynamic nature of proteins is often an underappreciated aspect of biology necessary for understanding protein function and turnover in the cell. This is in… (more)

▼ The dynamic nature of proteins is often an underappreciated aspect of biology necessary for understanding protein function and turnover in the cell. This is in part because within the multitude of states that a protein occupies throughout its lifetime, at most a few are significantly populated and have long enough lifetimes to study using traditional structural biology methods. In this thesis, I develop and explore experimental methods (amide hydrogen-deuterium exchange and cysteine labeling) to selectively label and characterize these rare and transient conformations methods. Specifically, I used cysteine labeling as a means to validate computational predictions of rare conformational fluctuations that expose potential drug-binding sites, I used pulse-labeling amide hydrogen exchange coupled with mass spectrometry detection to identify intermediates formed during protein folding and developed new data analysis procedures for analyzing hydrogen exchange rates measured determined by mass spectrometry on proteolytic fragments. The first project used thiol labeling rates to validate computational predictions of cryptic binding sites. Analysis of millisecond-long molecular dynamics (MD) simulations of β-lactamase uncovered several potential conformational fluctuations that expose hidden, or cryptic binding pockets. Targeting these rare conformations presents a potential avenue for drug development. I validated the existence of these pockets by introducing cysteine residues in select positions and characterizing their accessibility to chemical modifications. In addition to validating the existence of these fluctuations, modification of cysteines at these sites modulates activity allosterically.In the second project, I used pulsed labeling hydrogen exchange to follow the folding pathway of a protein family over evolutionary time (>3 billion years). I determined the conformations populated during folding (folding intermediates) for a family of RNase H proteins, including two extant and seven ancestral proteins. Each of these proteins was shown to populate a similar folding intermediate prior to the rate-limiting step in folding; however, the details of the steps leading up to this intermediate varied. We further showed that we can alter these early folding steps for a given protein using rationally designed mutations.The third project compared and characterized the refolding and co-translational folding pathway of the protein HaloTag. We found that HaloTag aggregates during refolding but not during cotranslational folding, and it adopts at least one intermediate during refolding that is suppressed during cotranslational folding.Finally, in the fourth project I developed a modification of a recently published approach for analyzing data from mass spectrometry-based detection of hydrogen exchange. This modification allows me to obtain multiple protection factors per peptide monitored and obtain a quantitative measurement of the free energy of hydrogen exchange in different regions of the protein.

Subjects/Keywords: Biophysics; Hydrogen Exchange; Protein Dynamics; Protein Folding

10 more images…

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Bolin, E. (2018). Characterizing rare and transient conformations of proteins using amide hydrogen exchange and thiol exchange. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/1cd158xw

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):

Bolin, Eric. “Characterizing rare and transient conformations of proteins using amide hydrogen exchange and thiol exchange.” 2018. Thesis, University of California – Berkeley. Accessed January 17, 2021. http://www.escholarship.org/uc/item/1cd158xw.

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

MLA Handbook (7^th Edition):

Bolin, Eric. “Characterizing rare and transient conformations of proteins using amide hydrogen exchange and thiol exchange.” 2018. Web. 17 Jan 2021.

Vancouver:

Bolin E. Characterizing rare and transient conformations of proteins using amide hydrogen exchange and thiol exchange. [Internet] [Thesis]. University of California – Berkeley; 2018. [cited 2021 Jan 17]. Available from: http://www.escholarship.org/uc/item/1cd158xw.

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

Council of Science Editors:

Bolin E. Characterizing rare and transient conformations of proteins using amide hydrogen exchange and thiol exchange. [Thesis]. University of California – Berkeley; 2018. Available from: http://www.escholarship.org/uc/item/1cd158xw

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. Unarta, Ilona Christy. Elucidating protein dynamics and protein-protein interactions using computer modeling and simulations.

Degree: 2017, Hong Kong University of Science and Technology

URL: http://repository.ust.hk/ir/Record/1783.1-88414 ; https://doi.org/10.14711/thesis-991012536069503412 ; http://repository.ust.hk/ir/bitstream/1783.1-88414/1/th_redirect.html

► Biological molecules are complex molecules typically consisting of a few thousand atoms. These molecules interact and undergo conformational change to perform biological function. This thesis… (more)

Subjects/Keywords: Proteins ; Dynamics ; Computer simulation ; Protein-protein interactions

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Unarta, I. C. (2017). Elucidating protein dynamics and protein-protein interactions using computer modeling and simulations. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-88414 ; https://doi.org/10.14711/thesis-991012536069503412 ; http://repository.ust.hk/ir/bitstream/1783.1-88414/1/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):

Unarta, Ilona Christy. “Elucidating protein dynamics and protein-protein interactions using computer modeling and simulations.” 2017. Thesis, Hong Kong University of Science and Technology. Accessed January 17, 2021. http://repository.ust.hk/ir/Record/1783.1-88414 ; https://doi.org/10.14711/thesis-991012536069503412 ; http://repository.ust.hk/ir/bitstream/1783.1-88414/1/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):

Unarta, Ilona Christy. “Elucidating protein dynamics and protein-protein interactions using computer modeling and simulations.” 2017. Web. 17 Jan 2021.

Vancouver:

Unarta IC. Elucidating protein dynamics and protein-protein interactions using computer modeling and simulations. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2017. [cited 2021 Jan 17]. Available from: http://repository.ust.hk/ir/Record/1783.1-88414 ; https://doi.org/10.14711/thesis-991012536069503412 ; http://repository.ust.hk/ir/bitstream/1783.1-88414/1/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:

Unarta IC. Elucidating protein dynamics and protein-protein interactions using computer modeling and simulations. [Thesis]. Hong Kong University of Science and Technology; 2017. Available from: http://repository.ust.hk/ir/Record/1783.1-88414 ; https://doi.org/10.14711/thesis-991012536069503412 ; http://repository.ust.hk/ir/bitstream/1783.1-88414/1/th_redirect.html

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

4. Nakagawa, Hiroshi. Neutron incoherent scattering studies on protein dynamics : タンパク質動力学の中性子非干渉性散乱による研究; タンパクシツドウリキガクノチュウセイシヒカンショウセイサンランニヨルケンキュウ.

Degree: Nara Institute of Science and Technology / 奈良先端科学技術大学院大学

URL: http://hdl.handle.net/10061/4011

Subjects/Keywords: Protein dynamics

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Nakagawa, H. (n.d.). Neutron incoherent scattering studies on protein dynamics : タンパク質動力学の中性子非干渉性散乱による研究; タンパクシツドウリキガクノチュウセイシヒカンショウセイサンランニヨルケンキュウ. (Thesis). Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Retrieved from http://hdl.handle.net/10061/4011

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nakagawa, Hiroshi. “Neutron incoherent scattering studies on protein dynamics : タンパク質動力学の中性子非干渉性散乱による研究; タンパクシツドウリキガクノチュウセイシヒカンショウセイサンランニヨルケンキュウ.” Thesis, Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Accessed January 17, 2021. http://hdl.handle.net/10061/4011.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nakagawa, Hiroshi. “Neutron incoherent scattering studies on protein dynamics : タンパク質動力学の中性子非干渉性散乱による研究; タンパクシツドウリキガクノチュウセイシヒカンショウセイサンランニヨルケンキュウ.” Web. 17 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Nakagawa H. Neutron incoherent scattering studies on protein dynamics : タンパク質動力学の中性子非干渉性散乱による研究; タンパクシツドウリキガクノチュウセイシヒカンショウセイサンランニヨルケンキュウ. [Internet] [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10061/4011.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

Nakagawa H. Neutron incoherent scattering studies on protein dynamics : タンパク質動力学の中性子非干渉性散乱による研究; タンパクシツドウリキガクノチュウセイシヒカンショウセイサンランニヨルケンキュウ. [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; Available from: http://hdl.handle.net/10061/4011

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

University of Otago

5. Campbell, Eugene. Comparison of FRET probes of conformational changes in DnaK and Hsc70 .

Degree: University of Otago

URL: http://hdl.handle.net/10523/8526

► Hsp70s are one of the most well conserved protein families known, yet little of their in vivo activity is understood and experimental resources required to… (more)

▼ Hsp70s are one of the most well conserved protein families known, yet little of their in vivo activity is understood and experimental resources required to investigate their activity. All Hsp70s are made up of two highly conserved functional domains joined by a flexible linker, the nucleotide binding domain and the substrate binding domain. The Hsp70 proteins undergo a conformational in their peptide binding and release cycle, with conformation of the protein determined by the nucleotide bound in the nucleotide binding domain. This study compared the two most wildly studied Hsp70 proteins, DnaK and the human Hsc70, HSPA8. Hsc70 is a constitutively expressed member of the Hsp70 family which has many roles within the cell, assisting with folding of nascent polypeptides, targeting proteins for degradation and translocating proteins to the endoplasmic reticulum. Both proteins were purified from bacterial expression systems and the purification of Hsc70 was improved by the addition of an additional isocratic step during ion exchange chromatography. Efficiency of labelling with fluorescent dyes was improved and the activity cycle of DnaK and Hsc70 directly compared. Of the eight variants tested only two, DnaK variant C16S/K321C/E430C and Hsc70 variant E318C/T427C/C574S/C603S showed changes in FRET efficiency in response to different nucleotides. In order to validate these variants as suitable models and to probe why other variants showed no changes in FRET efficiency, proteins were analysed for their protein refolding activity. An improved luciferase refolding assay was developed to analyse the rate of protein refolding for each of the Hsc70 and DnaK variants. All of the variants for both DnaK and Hsc70 retained protein refolding activity, however most were less efficient than the wild type protein, showing between 20 to 100% of the wild type proteins activity. This study identified Hsc70 variant E318C/T427C/C574S/C603S as a suitable candidate for future in vivo fluorescence assay of Hsc70 function. Advisors/Committee Members: Wilbanks, Sigurd (advisor).

Subjects/Keywords: Protein; dynamics

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Campbell, E. (n.d.). Comparison of FRET probes of conformational changes in DnaK and Hsc70 . (Masters Thesis). University of Otago. Retrieved from http://hdl.handle.net/10523/8526

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Chicago Manual of Style (16^th Edition):

Campbell, Eugene. “Comparison of FRET probes of conformational changes in DnaK and Hsc70 .” Masters Thesis, University of Otago. Accessed January 17, 2021. http://hdl.handle.net/10523/8526.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

MLA Handbook (7^th Edition):

Campbell, Eugene. “Comparison of FRET probes of conformational changes in DnaK and Hsc70 .” Web. 17 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Campbell E. Comparison of FRET probes of conformational changes in DnaK and Hsc70 . [Internet] [Masters thesis]. University of Otago; [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10523/8526.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Council of Science Editors:

Campbell E. Comparison of FRET probes of conformational changes in DnaK and Hsc70 . [Masters Thesis]. University of Otago; Available from: http://hdl.handle.net/10523/8526

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Iowa State University

6. Dotas, Rochelle Rea. Characterization of the C-terminal binding domain from bacterial Enzyme I.

Degree: 2020, Iowa State University

URL: https://lib.dr.iastate.edu/etd/17981

► Modulation of enzyme structure and flexibility by substrate/ligand binding provides an important source of enzyme function regulation. Unfortunately, our understanding of the fundamental mechanisms coupling… (more)

▼ Modulation of enzyme structure and flexibility by substrate/ligand binding provides an important source of enzyme function regulation. Unfortunately, our understanding of the fundamental mechanisms coupling protein dynamics to biological function is still largely incomplete, therefore limiting our ability to harness protein conformational dynamics in order to regulate enzymatic activity. Here we couple variable temperature (VT) NMR, particularly relaxation dispersion experiments, X-ray crystallography, computer simulations, protein engineering, and enzyme kinetic assays to explore the role of structural heterogeneity and conformational disorder in regulation of the C-terminal substrate binding domain (EIC) of bacterial Enzyme I (EI). In particular, we investigate the relationship between structure, conformational dynamics, and biological function of four EIC constructs: the wild type mesophilic enzyme (eEIC), a thermophilic homologue (tEIC), and two hybrid constructs engineered by incorporating the active site loops of the mesophilic enzyme into the scaffold of the thermophilic enzyme (etEIC), and vice versa (teEIC). Through this characterization we provide evidence that the four EIC constructs are structurally similar and that holo EIC undergoes an exchange between a disordered expanded inactive state and a more ordered compact active state. Furthermore, we report that the population of the active state dictates the effective turnover number and that this functional regulation is achieved by tuning the thermodynamic balance between the active and inactive states providing rational for thermal adaption (i.e. why thermophilic homologues exhibit lower activity than their mesophilic counterpart at low temperatures but increased activity comparable to its mesophilic homologue at higher temperatures). We demonstrate that altering thermal stability, conformational flexibility, and enzymatic activity through the hybridization of mesophilic/thermophilic enzyme pairs is a promising strategy for protein engineering in the field of biotechnology.

Subjects/Keywords: Dynamics; Enzyme; Kinetics; NMR; Protein

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Dotas, R. R. (2020). Characterization of the C-terminal binding domain from bacterial Enzyme I. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/17981

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):

Dotas, Rochelle Rea. “Characterization of the C-terminal binding domain from bacterial Enzyme I.” 2020. Thesis, Iowa State University. Accessed January 17, 2021. https://lib.dr.iastate.edu/etd/17981.

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

MLA Handbook (7^th Edition):

Dotas, Rochelle Rea. “Characterization of the C-terminal binding domain from bacterial Enzyme I.” 2020. Web. 17 Jan 2021.

Vancouver:

Dotas RR. Characterization of the C-terminal binding domain from bacterial Enzyme I. [Internet] [Thesis]. Iowa State University; 2020. [cited 2021 Jan 17]. Available from: https://lib.dr.iastate.edu/etd/17981.

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

Council of Science Editors:

Dotas RR. Characterization of the C-terminal binding domain from bacterial Enzyme I. [Thesis]. Iowa State University; 2020. Available from: https://lib.dr.iastate.edu/etd/17981

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

Rice University

7. Hruska, Eugen. Adaptive sampling of Conformational Dynamics.

Degree: PhD, Natural Sciences, 2020, Rice University

URL: http://hdl.handle.net/1911/108744

► At the core of our limited ability to understand many biophysical processes is the challenge of predicting the conformational dynamics of biomolecules. This challenge includes… (more)

▼ At the core of our limited ability to understand many biophysical processes is the challenge of predicting the conformational dynamics of biomolecules. This challenge includes many open questions around the biophysical causes of many diseases or open questions in biophysics theory. Adaptive sampling is an approach to increase our ability to predict conformational dynamics. Adaptive sampling is a class of sampling strategies, where an ensemble of molecular dynamics trajectories is generated, where the starting points for the individual trajectories depend on the previously simulated trajectories. This approach will be investigated in this thesis. The application of adaptive sampling to biomolecules is one example of the more general problem of accurately sampling the time-dynamics of high-dimensional stochastic systems. The high-dimensionality, combined with a complex energy landscape, impede simpler approaches. Due to the broad scope of the general challenge, this Dissertation will focus only on improving the prediction of conformational dynamics for proteins. Many previous approaches to unravel this challenge have achieved significant improvements. In the case of proteins, the timescales where we can predict the conformational dynamics have increased by many orders of magnitudes to the millisecond scale. Despite the improvements, the current state-of-art can only predict the accurate behavior for small proteins. This illustrates the magnitude of the challenge. For most of the larger biomolecules, we are not able to simulate the precise behavior. This is not only caused by the several magnitudes longer timescales for these larger systems but also an order of magnitude larger sizes of these biomolecules. In this thesis, the adaptive sampling of conformational dynamics will be investigated in several steps. First, the prediction of the effectivity of different adaptive sampling strategies will be discussed. Due to significant stochasticity and protein-to-protein variation, the choice of adaptive sampling strategy is not apparent. The performance of different strategies for different goals varies as well. Second, to deepen our theoretical understanding of adaptive sampling strategies, an upper limit for the performance of any adaptive sampling strategy is developed. This theoretical upper limit allows us to understand the potential and limits of adaptive sampling. Third, adaptive sampling is heavily dependent on software due to the necessary thousands or millions of individual steps. All these steps have to be executed efficiently on a High-Performance Computer (HPC). Here we show the development of the software package ExTASY. This framework allows performing all the necessary steps in adaptive sampling while reducing the workload. The innovations of ExTASY are both the high-scalability and the modularity. The modularity allows for an easy change of the adaptive sampling strategies and better maintainability. ExTASY is reducing the entry barrier to utilizing adaptive sampling. Finally, the package ExTASY… Advisors/Committee Members: Clementi, Cecilia (advisor), Onuchic, Jose (advisor).

Subjects/Keywords: protein folding; molecular dynamics

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Hruska, E. (2020). Adaptive sampling of Conformational Dynamics. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/108744

Chicago Manual of Style (16^th Edition):

Hruska, Eugen. “Adaptive sampling of Conformational Dynamics.” 2020. Doctoral Dissertation, Rice University. Accessed January 17, 2021. http://hdl.handle.net/1911/108744.

MLA Handbook (7^th Edition):

Hruska, Eugen. “Adaptive sampling of Conformational Dynamics.” 2020. Web. 17 Jan 2021.

Vancouver:

Hruska E. Adaptive sampling of Conformational Dynamics. [Internet] [Doctoral dissertation]. Rice University; 2020. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1911/108744.

Council of Science Editors:

Hruska E. Adaptive sampling of Conformational Dynamics. [Doctoral Dissertation]. Rice University; 2020. Available from: http://hdl.handle.net/1911/108744

University of Waterloo

8. Trainor, Kyle. Adnectin Solubility and Dynamics.

Degree: 2019, University of Waterloo

URL: http://hdl.handle.net/10012/15234

► Rapid growth of the global market for monoclonal antibodies (mAbs) has generated considerable interest in the development of alternative molecules that facilitate rapid discovery and… (more)

▼ Rapid growth of the global market for monoclonal antibodies (mAbs) has generated considerable interest in the development of alternative molecules that facilitate rapid discovery and manufacturing, while replicating the low toxicity/immunogenicity and tight, specific binding of mAbs. One such molecule is the tenth human fibronectin type III domain (10Fn3), which has solvent accessible loops resembling the VH complementarity-determining regions H1, H2, and H3 of immunoglobulin. 10Fn3-based binding proteins called Adnectins have been engineered to bind with high affinity to diverse targets using in vitro evolution methods such as mRNA display, yeast display, and phage display. Adnectins are known to vary in aggregation propensity, sometimes despite exceptionally high amino acid sequence identity, and have been used as a basis for protein aggregation/solubility research. Aggregation of therapeutic proteins can provoke a protein-specific immune response, and the solubility of Adnectins is therefore of immediate practical interest. The aggregation of proteins in general is a complicated and incompletely understood phenomenon, the study of which we advance using Adnectins as a model system. We also investigate protein dynamics (which can be related to protein aggregation, but additionally has enormous impact on how we think about protein structure and function) through nuclear magnetic resonance (NMR) spectroscopic and computational study of Adnectins. Here, we first present solubility data for a reference set of 41 Adnectins and use them to screen computational solubility/aggregation prediction methods. On the basis of these results, we select the CamSol prediction method for use in a protein engineering project that applies the principles of consensus design to enhance the solubility of the Adnectin scaffold. Furthermore, we demonstrate that hydrogen/deuterium exchange by hydrogen bonded amides in the C-terminal β-strand of the original scaffold is induced by transient inter-Adnectin association, and that equivalent exchange is not observed in our solubility-enhanced scaffold. Next, we describe the results of variable-temperature solution NMR experiments that probe Adnectin dynamics. Each resonance observable by NMR spectroscopy is composed of contributions from structurally equivalent nuclei in a vast number of proteins, the conformations of which may both differ from each other at any particular instant and evolve over the timescale of the experiment. The temperature dependences of amide proton and nitrogen chemical shifts are due to differences in the conformations sampled and their probabilities of occupation. Empirically, these temperature dependences are well-approximated by fits to a linear model, the slopes of which (known as temperature coefficients) may report on protein dynamics in the vicinity of each backbone amide. We explore possible determinants of amide proton and nitrogen temperature coefficients using a combination of molecular dynamics simulations and quantum chemical (density functional…

Subjects/Keywords: protein; aggregation; solubility; dynamics; Adnectin

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Trainor, K. (2019). Adnectin Solubility and Dynamics. (Thesis). University of Waterloo. Retrieved from http://hdl.handle.net/10012/15234

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):

Trainor, Kyle. “Adnectin Solubility and Dynamics.” 2019. Thesis, University of Waterloo. Accessed January 17, 2021. http://hdl.handle.net/10012/15234.

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

MLA Handbook (7^th Edition):

Trainor, Kyle. “Adnectin Solubility and Dynamics.” 2019. Web. 17 Jan 2021.

Vancouver:

Trainor K. Adnectin Solubility and Dynamics. [Internet] [Thesis]. University of Waterloo; 2019. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10012/15234.

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

Council of Science Editors:

Trainor K. Adnectin Solubility and Dynamics. [Thesis]. University of Waterloo; 2019. Available from: http://hdl.handle.net/10012/15234

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

University of Tennessee – Knoxville

9. Bernal Gomez, Ana Virginia. Conformational Dynamics of Cytochrome P450cam Upon Ligand Binding.

Degree: MS, Biochemistry and Cellular and Molecular Biology, 2015, University of Tennessee – Knoxville

URL: https://trace.tennessee.edu/utk_gradthes/3440

► Cytochrome P450s are a superfamily of metalloenzymes that are responsible for the monooxygenation of their hydrophobic substrates. P450’s retain the same general structural scaffold,… (more)

Subjects/Keywords: protein; dynamics; cytochrome; Biochemistry

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Bernal Gomez, A. V. (2015). Conformational Dynamics of Cytochrome P450cam Upon Ligand Binding. (Thesis). University of Tennessee – Knoxville. Retrieved from https://trace.tennessee.edu/utk_gradthes/3440

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):

Bernal Gomez, Ana Virginia. “Conformational Dynamics of Cytochrome P450cam Upon Ligand Binding.” 2015. Thesis, University of Tennessee – Knoxville. Accessed January 17, 2021. https://trace.tennessee.edu/utk_gradthes/3440.

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

MLA Handbook (7^th Edition):

Bernal Gomez, Ana Virginia. “Conformational Dynamics of Cytochrome P450cam Upon Ligand Binding.” 2015. Web. 17 Jan 2021.

Vancouver:

Bernal Gomez AV. Conformational Dynamics of Cytochrome P450cam Upon Ligand Binding. [Internet] [Thesis]. University of Tennessee – Knoxville; 2015. [cited 2021 Jan 17]. Available from: https://trace.tennessee.edu/utk_gradthes/3440.

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

Council of Science Editors:

Bernal Gomez AV. Conformational Dynamics of Cytochrome P450cam Upon Ligand Binding. [Thesis]. University of Tennessee – Knoxville; 2015. Available from: https://trace.tennessee.edu/utk_gradthes/3440

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

University of Illinois – Urbana-Champaign

10. Zhang, Yi. Frustration of protein folding from in vitro to in vivo.

Degree: PhD, Biophysics & Computnl Biology, 2018, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/101788

► Protein folding, a ubiquitous and vital biological process, where protein random coil transforms into certain conformation in order to fulfill its function. Misfolded protein which… (more)

▼ Protein folding, a ubiquitous and vital biological process, where protein random coil transforms into certain conformation in order to fulfill its function. Misfolded protein which fails to acquire proper shape, not only loses its function, but can also cause fatal diseases. In this dissertation, I will present four case studies involving protein folding investigated through computational modeling and molecular dynamics (MD) simulations. All projects are closely related to experiments, demonstrating the unique role of MD simulations in providing insightful molecular details, testing experimental hypothesis as well as predicting new directions for experimentalists. A brief overview of each chapter is summarized here: Chapter 1 gives brief background information on each of the four project as well as a general introduction on MD simulations, the core methodology used throughout the dissertation. Chapter 2 reports work on a fast protein folder named λ-repressor, where we aim to investigate the different folding kinetics between three mutants of λ-repressor observed in experiments and compare experiments with simulations. Chapter 3 presents protein frustration by disulfide bridges in collaboration with Prof. Norelle Daly’s Lab in Australia. We examined a small cysteine-rich cyclic peptide named MCoTI-II and showed that frustration between certain cysteine residues could impede its folding. Chapter 4 details the construction of an atomic model of cytoplasm and explores the folding of a fast-folding protein (WW domain variant) in a cell-like environment. Chapter 5 reports work on protein recognition by the proteasome, where we investigated protein waste recycling in cells and found that protein re-folding is a vital process in 26S proteasome to initiate protein degradation . Advisors/Committee Members: Pogorelov, Taras (advisor), Gruebele, Martin (Committee Chair), Luthey-Schulten, Zan (committee member), Rienstra, Chad (committee member), Shukla, Diwakar (committee member).

Subjects/Keywords: protein folding; molecular dynamics

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Zhang, Y. (2018). Frustration of protein folding from in vitro to in vivo. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/101788

Chicago Manual of Style (16^th Edition):

Zhang, Yi. “Frustration of protein folding from in vitro to in vivo.” 2018. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 17, 2021. http://hdl.handle.net/2142/101788.

MLA Handbook (7^th Edition):

Zhang, Yi. “Frustration of protein folding from in vitro to in vivo.” 2018. Web. 17 Jan 2021.

Vancouver:

Zhang Y. Frustration of protein folding from in vitro to in vivo. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2018. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/2142/101788.

Council of Science Editors:

Zhang Y. Frustration of protein folding from in vitro to in vivo. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2018. Available from: http://hdl.handle.net/2142/101788

University of Montana

11. Black, Labe Adam. DYNAMIC MOTIONS OF THE ALPHA SUBUNIT OF HETEROTRIMERIC G PROTEINS IN THE NUCLEOTIDE- AND RIC-8A-BOUND STATES.

Degree: PhD, 2015, University of Montana

URL: https://scholarworks.umt.edu/etd/4610

► The conformational changes and segmental dynamics involved in the G alpha-subunit of heterotrimeric G proteins have been investigated for 3 separate binding states by using… (more)

Subjects/Keywords: dynamics; G protein; Ric-8A

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Black, L. A. (2015). DYNAMIC MOTIONS OF THE ALPHA SUBUNIT OF HETEROTRIMERIC G PROTEINS IN THE NUCLEOTIDE- AND RIC-8A-BOUND STATES. (Doctoral Dissertation). University of Montana. Retrieved from https://scholarworks.umt.edu/etd/4610

Chicago Manual of Style (16^th Edition):

Black, Labe Adam. “DYNAMIC MOTIONS OF THE ALPHA SUBUNIT OF HETEROTRIMERIC G PROTEINS IN THE NUCLEOTIDE- AND RIC-8A-BOUND STATES.” 2015. Doctoral Dissertation, University of Montana. Accessed January 17, 2021. https://scholarworks.umt.edu/etd/4610.

MLA Handbook (7^th Edition):

Black, Labe Adam. “DYNAMIC MOTIONS OF THE ALPHA SUBUNIT OF HETEROTRIMERIC G PROTEINS IN THE NUCLEOTIDE- AND RIC-8A-BOUND STATES.” 2015. Web. 17 Jan 2021.

Vancouver:

Black LA. DYNAMIC MOTIONS OF THE ALPHA SUBUNIT OF HETEROTRIMERIC G PROTEINS IN THE NUCLEOTIDE- AND RIC-8A-BOUND STATES. [Internet] [Doctoral dissertation]. University of Montana; 2015. [cited 2021 Jan 17]. Available from: https://scholarworks.umt.edu/etd/4610.

Council of Science Editors:

Black LA. DYNAMIC MOTIONS OF THE ALPHA SUBUNIT OF HETEROTRIMERIC G PROTEINS IN THE NUCLEOTIDE- AND RIC-8A-BOUND STATES. [Doctoral Dissertation]. University of Montana; 2015. Available from: https://scholarworks.umt.edu/etd/4610

12. Xu, Yao. Molecular Dynamics Simulation Studies on Interfacial Dynamics of Proteins.

Degree: 2013, University of Nevada – Reno

URL: http://hdl.handle.net/11714/3115

► Clusters of water molecules embedded in proteins or at the interface between globules mediate protein dynamics, allostery and charge transfer. Confined clusters of water molecules… (more)

Subjects/Keywords: Molecular Dynamics; Molecular Dynamics Simulation; Protein Dynamics; Protein-water Interactions; Vibrational Energy Flow; Water Dynamics

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Xu, Y. (2013). Molecular Dynamics Simulation Studies on Interfacial Dynamics of Proteins. (Thesis). University of Nevada – Reno. Retrieved from http://hdl.handle.net/11714/3115

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, Yao. “Molecular Dynamics Simulation Studies on Interfacial Dynamics of Proteins.” 2013. Thesis, University of Nevada – Reno. Accessed January 17, 2021. http://hdl.handle.net/11714/3115.

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, Yao. “Molecular Dynamics Simulation Studies on Interfacial Dynamics of Proteins.” 2013. Web. 17 Jan 2021.

Vancouver:

Xu Y. Molecular Dynamics Simulation Studies on Interfacial Dynamics of Proteins. [Internet] [Thesis]. University of Nevada – Reno; 2013. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/11714/3115.

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. Molecular Dynamics Simulation Studies on Interfacial Dynamics of Proteins. [Thesis]. University of Nevada – Reno; 2013. Available from: http://hdl.handle.net/11714/3115

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

University of Kansas

13. Rui, Huan. Computational Studies of Protein Structure, Dynamics, and Function in Native-like Environments.

Degree: PhD, Biochemistry & Molecular Biology, 2013, University of Kansas

URL: http://hdl.handle.net/1808/14217

► Proteins are among the four unique organic constituents of cells. They are responsible for a variety of important cell functions ranging from providing structural support… (more)

▼ Proteins are among the four unique organic constituents of cells. They are responsible for a variety of important cell functions ranging from providing structural support to catalyzing biological reactions. They vary in shape, dynamic behavior, and localization. All of these together determine the specificity in their functions, but the question is how. The ultimate goal of the research conducted in this thesis is to answer this question. Two types of proteins are of particular interest. They include transmembrane proteins and protein assemblies. Using computer simulations with available experimental data to validate the simulation results, the research described here aims to reveal the structure and dynamics of proteins in their native-like environment and the indication on the mechanism of their functions. The first part of the thesis focuses on studying the structure and functions of transmembrane proteins. These proteins are consisted of transmembrane α-helices or β-strands, and each of the secondary structure elements adopts a unique orientation in the membrane following its local interactions. The structure of the entire protein is a collection of the orientations of these elements and their relative positions with respect to one another. These two basic aspects of membrane protein structure are studied in Chapter II and III. In Chapter II, efforts are given to determine the favorable orientation of a β-hairpin peptide, protegrin-1, in different lipid bilayers. The orientational preference results from the interplay between the protein and the surrounding lipid molecules. Chapter III is centered on revealing the structure and dynamics of caveolin-1 in DMPC bilayers. Caveolin-1 forms a re-entrant helix-turn-helix structure with two α-helices embedded in the membrane bilayer. The study shows that caveolin-1 monomer is rather dynamic and maintains its inserted conformation via both specific and non-specific protein-lipid interactions. To investigate the structural and dynamic impact on the function of a membrane protein, molecular dynamics simulations of the voltage-dependent anion channel are performed and the results are presented in Chapter IV. It is found in this chapter that the electrostatic interactions between charged residues on the channel wall facing the lumen are responsible for retarding the cation current, therefore giving the channel its anion selectivity. The second category of protein that is of interest in this thesis is the assembled protein complex, especially the ones that are highly symmetric. Actually, many membrane proteins belong to this category as well, but the study presented here in Chapter V involves simulations performed on a soluble protein complex, bacterioferritin B from Pseudomonas Aeruginosa. It is revealed by the simulations that the dynamic behavior of the protein is magnified by the symmetry and is tightly associated to its function. Advisors/Committee Members: Im, Wonpil (advisor), Deeds, Eric (cmtemember), Karanicolas, John (cmtemember), Rivera, Mario (cmtemember), Vakser, Ilya (cmtemember).

Subjects/Keywords: Bioinformatics; Biophysics; Biochemistry; Membrane bilayers; Membrane protein; Molecular dynamics simulations; Protein assembly; Protein dynamics

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Rui, H. (2013). Computational Studies of Protein Structure, Dynamics, and Function in Native-like Environments. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/14217

Chicago Manual of Style (16^th Edition):

Rui, Huan. “Computational Studies of Protein Structure, Dynamics, and Function in Native-like Environments.” 2013. Doctoral Dissertation, University of Kansas. Accessed January 17, 2021. http://hdl.handle.net/1808/14217.

MLA Handbook (7^th Edition):

Rui, Huan. “Computational Studies of Protein Structure, Dynamics, and Function in Native-like Environments.” 2013. Web. 17 Jan 2021.

Vancouver:

Rui H. Computational Studies of Protein Structure, Dynamics, and Function in Native-like Environments. [Internet] [Doctoral dissertation]. University of Kansas; 2013. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1808/14217.

Council of Science Editors:

Rui H. Computational Studies of Protein Structure, Dynamics, and Function in Native-like Environments. [Doctoral Dissertation]. University of Kansas; 2013. Available from: http://hdl.handle.net/1808/14217

Indian Institute of Science

14. Katagi, Gurunath M. Analysis of Molecular Dynamics Trajectories of Proteins Performed using Different Forcefields and Identifiction of Mobile Segments.

Degree: MSc Engg, Faculty of Engineering, 2018, Indian Institute of Science

URL: http://etd.iisc.ac.in/handle/2005/3327

► The selection of the forcefield is a crucial issue in any MD related work and there is no clear indication as to which of the… (more)

▼ The selection of the forcefield is a crucial issue in any MD related work and there is no clear indication as to which of the many available forcefields is the best for protein analysis. Many recent literature surveys indicate that MD work may be hindered by two limitations, namely conformational sampling and forcefields used (inaccuracies in the potential energy function may bias the simulation toward incorrect conformations). However, the advances in computing infrastructures, theoretical and computing aspects of MD have paved the way to carry out a sampling on a sufficiently longtime scale, putting a need for the accuracies in the forcefield. Because there are established differences in MD results when using forcefields, we have sought to ask how we could assess common mobility segments from a protein by analysis of trajectories using three forcefields in a similar environment. This is important because, disparate fluctuations appear to be more at flexible regions compared to stiff regions; in particular, flexible regions are more relevant to functional activities of the protein molecule. Therefore, we have tried to assess the similarity in the dynamics using three well-known forcefields ENCAD, CHARMM27 and AMBERFF99SB for 61 monomeric proteins and identify the properties of dynamic residues, which may be important for function. The comparison of popular forcefields with different parameterization philosophy may give hints to improve some of the currently existing agnostics in forcefields and characterization of mobile regions based on dynamics of proteins with diverse folds. These may also give some signature on the proteins at the level of dynamics in relation to function, which can be used in protein engineering studies. Nanosecond level MD simulation(30ns) on 61 monomeric proteins were carried out using CHARMM and AMBER forcefields and the trajectories with ENCAD forcefield obtained from Dynameomics database. The trajectories were first analyzed to check whether structural and dynamic properties from the three forcefields similar choosing few parameters in each case. The gross dynamic properties calculated (root mean square deviation (RMSD), TM-score derived RMSD, radius of gyration and accessible surface area) indicated similarity in many proteins. Flexibility index analysis on 17 proteins, which showed a notable difference in the flexibility, indicated that tertiary interactions (fraction of nonnative stable hydrogen bonds and salt bridges) might be responsible for the difference in the flexibility index. The normalized subspace overlap and shape overlap score taken based on the covariance matrices derived from trajectories indicated that majority of the proteins show a range between 0.3-0.5 indicating that the first principal components from these proteins in different combinations may not match well. These results indicate that although dynamic properties in general are similar in many proteins. However, flexibility index and normalized subspace overlap score indicate that subspaces on the first… Advisors/Committee Members: Pal, Debnath (advisor).

Subjects/Keywords: Protein Structures; Protein Dynamics; Protein Functions; Proteins - Analysis; Proteins - Molecular Dynamics Simulations; Protein Flexibility; Protein Simulation Trajectories; Forcefields - Protein Analysis; Protein Structure - Computation; Molecular Dynamics Simulations; MD Simulations; Biochemistry

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Katagi, G. M. (2018). Analysis of Molecular Dynamics Trajectories of Proteins Performed using Different Forcefields and Identifiction of Mobile Segments. (Masters Thesis). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/3327

Chicago Manual of Style (16^th Edition):

Katagi, Gurunath M. “Analysis of Molecular Dynamics Trajectories of Proteins Performed using Different Forcefields and Identifiction of Mobile Segments.” 2018. Masters Thesis, Indian Institute of Science. Accessed January 17, 2021. http://etd.iisc.ac.in/handle/2005/3327.

MLA Handbook (7^th Edition):

Katagi, Gurunath M. “Analysis of Molecular Dynamics Trajectories of Proteins Performed using Different Forcefields and Identifiction of Mobile Segments.” 2018. Web. 17 Jan 2021.

Vancouver:

Katagi GM. Analysis of Molecular Dynamics Trajectories of Proteins Performed using Different Forcefields and Identifiction of Mobile Segments. [Internet] [Masters thesis]. Indian Institute of Science; 2018. [cited 2021 Jan 17]. Available from: http://etd.iisc.ac.in/handle/2005/3327.

Council of Science Editors:

Katagi GM. Analysis of Molecular Dynamics Trajectories of Proteins Performed using Different Forcefields and Identifiction of Mobile Segments. [Masters Thesis]. Indian Institute of Science; 2018. Available from: http://etd.iisc.ac.in/handle/2005/3327

Indian Institute of Science

15. Adkar, Bharat V. Computational And Experimental Studies On Protein Structure, Stability And Dynamics.

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

URL: http://etd.iisc.ac.in/handle/2005/2369

► The work in this thesis focuses on the study of three main aspects of proteins, viz, Protein structure, stability, and dynamics. Chapter 1 is a… (more)

▼ The work in this thesis focuses on the study of three main aspects of proteins, viz, Protein structure, stability, and dynamics. Chapter 1 is a general introduction to the topics studied in this thesis. Chapter 2 deals with the first aspect, i.e., protein structure in which we describe an approach to use saturation mutagenesis phenotypes to guide protein structure prediction. Chapters 3 and 4 discuss how to increase protein stability using surface electrostatics, and Chapter 5 details a method to predict whether a proline substitution in a given protein would be stabilizing or destabilizing. Hence, Chapters 3-5 can be associated with the second aspect, i.e., protein stability. The third aspect, namely protein dynamics, is dealt with in Chapters 6 and 7 which study conformational dynamics of adenylate kinase. Protein structure prediction is a difficult problem with two major bottlenecks, namely, generation of accurate models and the selection of the most appropriate models from a large pool of decoys. In Chapter 2, the problem of model discrimination is addressed using mutant phenotype information derived from saturation mutagenesis library. A library of ~1500 single-site mutants of the E. coli toxin CcdB (Controller of Cell Division or Death B) has been previously constructed in our lab. The pooled library was characterized in terms of individual mutant phenotypes at various expression levels which were derived from the relative populations of mutants at each expression level. The relative populations of mutants were estimated using deep sequencing. Mutational tolerances were derived from the phenotypic data and were used to define an empirical parameter which correlated with a structural parameter, residue depth. We further studied how this new parameter can be used for model discrimination. Increasing protein stability in a rational way is a challenging problem and has been addressed by various approaches. One of the most commonly used approaches is optimization of protein core residues. Recently, optimization of protein surface electrostatics has been shown to be a useful approach for increasing stability of proteins. In Chapter 3, from analyses of a dataset of ~1750 non-homologues proteins, we show that proteins having a pI away from physiological pH, possess a significant fraction of unfavorably placed charged amino acids on their surface. One way to increase protein stability in such cases might be to alter these surface charges. This hypothesis was validated experimentally by making charge reversal mutations at putative unfavorable positions on the surface of maltose binding protein, MBP. The observed stabilization can potentially be increased by combining multiple individually stabilizing mutations. Different combinations of such mutations were made and tested in Chapter 4 to decide which mutants can be combined to achieve net stabilization. Ideas were tested through systematic experimentation which involved generation of two-site, three-site, and four-site mutations. A maximum increase in melting… Advisors/Committee Members: Varadarajan, Raghavan (advisor), Bagchi, Biman (advisor).

Subjects/Keywords: Proteins; Protein Structure; Protein Stability; Protein Dynamics; Protein Surface Electrostatics; Adenylate Kinase; Proline Mutations; Biochemistry

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Adkar, B. V. (2014). Computational And Experimental Studies On Protein Structure, Stability And Dynamics. (Doctoral Dissertation). Indian Institute of Science. Retrieved from http://etd.iisc.ac.in/handle/2005/2369

Chicago Manual of Style (16^th Edition):

Adkar, Bharat V. “Computational And Experimental Studies On Protein Structure, Stability And Dynamics.” 2014. Doctoral Dissertation, Indian Institute of Science. Accessed January 17, 2021. http://etd.iisc.ac.in/handle/2005/2369.

MLA Handbook (7^th Edition):

Adkar, Bharat V. “Computational And Experimental Studies On Protein Structure, Stability And Dynamics.” 2014. Web. 17 Jan 2021.

Vancouver:

Adkar BV. Computational And Experimental Studies On Protein Structure, Stability And Dynamics. [Internet] [Doctoral dissertation]. Indian Institute of Science; 2014. [cited 2021 Jan 17]. Available from: http://etd.iisc.ac.in/handle/2005/2369.

Council of Science Editors:

Adkar BV. Computational And Experimental Studies On Protein Structure, Stability And Dynamics. [Doctoral Dissertation]. Indian Institute of Science; 2014. Available from: http://etd.iisc.ac.in/handle/2005/2369

University of Ottawa

16. Davey, James A. Multistate Computational Protein Design: Theories, Methods, and Applications .

Degree: 2016, University of Ottawa

URL: http://hdl.handle.net/10393/35541

► Traditional computational protein design (CPD) calculations model sequence perturbations and evaluate their stabilities using a single fixed protein backbone template in an approach referred to… (more)

Subjects/Keywords: computational protein design; multistate design; protein engineering; molecular modeling; substrate multispecificity; protein stability; protein dynamics

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Davey, J. A. (2016). Multistate Computational Protein Design: Theories, Methods, and Applications . (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/35541

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):

Davey, James A. “Multistate Computational Protein Design: Theories, Methods, and Applications .” 2016. Thesis, University of Ottawa. Accessed January 17, 2021. http://hdl.handle.net/10393/35541.

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

MLA Handbook (7^th Edition):

Davey, James A. “Multistate Computational Protein Design: Theories, Methods, and Applications .” 2016. Web. 17 Jan 2021.

Vancouver:

Davey JA. Multistate Computational Protein Design: Theories, Methods, and Applications . [Internet] [Thesis]. University of Ottawa; 2016. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10393/35541.

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

Council of Science Editors:

Davey JA. Multistate Computational Protein Design: Theories, Methods, and Applications . [Thesis]. University of Ottawa; 2016. Available from: http://hdl.handle.net/10393/35541

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

University of Manchester

17. Stewart, Andrew. Conformational Mapping of Dynamic Protein Systems by PELDOR Spectroscopy.

Degree: 2018, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:317701

► Understanding the relationship between protein structure and function remains a large challenge in protein biochemistry. In particular, large multi-domain proteins pose challenges for determining their… (more)

Subjects/Keywords: protein; dynamics; EPR; DEER; PELDOR; calmodulin

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Stewart, A. (2018). Conformational Mapping of Dynamic Protein Systems by PELDOR Spectroscopy. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:317701

Chicago Manual of Style (16^th Edition):

Stewart, Andrew. “Conformational Mapping of Dynamic Protein Systems by PELDOR Spectroscopy.” 2018. Doctoral Dissertation, University of Manchester. Accessed January 17, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:317701.

MLA Handbook (7^th Edition):

Stewart, Andrew. “Conformational Mapping of Dynamic Protein Systems by PELDOR Spectroscopy.” 2018. Web. 17 Jan 2021.

Vancouver:

Stewart A. Conformational Mapping of Dynamic Protein Systems by PELDOR Spectroscopy. [Internet] [Doctoral dissertation]. University of Manchester; 2018. [cited 2021 Jan 17]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:317701.

Council of Science Editors:

Stewart A. Conformational Mapping of Dynamic Protein Systems by PELDOR Spectroscopy. [Doctoral Dissertation]. University of Manchester; 2018. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:317701

Penn State University

18. Fortunato, Michael Edward. Immunoglobulin G: Solution Dynamics, Carbohydrate Structure, and Self-association From Atomistic and Coarse-grained Simulations.

Degree: 2015, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/24261

► Immunoglobulin molecules are extremely effective at providing protection from foreign molecules or viruses; however, in certain cases the naturally occurring immune system cannot provide adequate… (more)

▼ Immunoglobulin molecules are extremely effective at providing protection from foreign molecules or viruses; however, in certain cases the naturally occurring immune system cannot provide adequate protection. Monoclonal antibodies are designed to fill these gaps by engineering antigen binding regions capable of targeting and eliminating dangerous molecules. The monoclonal antibodies can function when isolated and able to travel through the blood stream. However, immunoglobulin efficiency decreases upon self-association for two reasons. First, the immune system may recognize the associated molecules and eliminate them depending on the size of the aggregates. Second, if the molecules associate in such a way that the antigen binding regions are no longer accessible they will be unable to function. This thesis discusses molecular simulation techniques that can be used to study the structural changes that occur due to intrinsic molecular flexibility in immunoglobulin molecules as well as the structure of small aggregates that form through self-association. One solvated immunoglobulin molecule was studied by explicitly representing every atom however coarse-graining techniques were required in order to study multiple molecules in the same system. The role of terminal galactose residues in the carbohydrate attached to the Fc domain in an atomisitc model of an antibody molecule was studied in this work. Carbohydrate mobility as well as the protein–carbohydrate hydrogen bonding interactions were compared between simulations with and without terminal galactose residues. It was shown that one of the two biantennary terminal galactose residues preferentially interacts with the protein when both were present; however, when both were removed the carbohydrate structure changed such that new protein–carbohydrate interactions formed. This change in solvent accessible protein surfaces will be an important area of study to both increase effector functions and decrease self-association involving the Fc domain. Understanding through which residues immunoglobulin molecules interact will lead to better designed monoclonal antibodies with increased aggregation resistance. To aid in this understanding, a previously developed residue level coarse-grained model was employed using the same model molecule from the previous atomistic studies. The residues most often involved in self-association of the antibody were individually mutated to alanine and the resulting association frequencies were compared to the “native” immunoglobulin results to determine the residues most important in self-association. Because of the asymmetry in the three-dimensional structure of the model immunoglobulin molecule used in this work, differences in aggregation behavior between two domains with identical amino acid sequence indicated that molecular structure can play a significant role in self-association. These simulation techniques were shown to be effective at studying molecular flexibility and protein–carbohydrate interactions with great chemical detail as well as… Advisors/Committee Members: Coray M Colina, Thesis Advisor/Co-Advisor, Scott A Showalter, Thesis Advisor/Co-Advisor, Ralph H Colby, Thesis Advisor/Co-Advisor.

Subjects/Keywords: IgG; protein; simulation; molecular; dynamics; carbohydrate

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Fortunato, M. E. (2015). Immunoglobulin G: Solution Dynamics, Carbohydrate Structure, and Self-association From Atomistic and Coarse-grained Simulations. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/24261

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):

Fortunato, Michael Edward. “Immunoglobulin G: Solution Dynamics, Carbohydrate Structure, and Self-association From Atomistic and Coarse-grained Simulations.” 2015. Thesis, Penn State University. Accessed January 17, 2021. https://submit-etda.libraries.psu.edu/catalog/24261.

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

MLA Handbook (7^th Edition):

Fortunato, Michael Edward. “Immunoglobulin G: Solution Dynamics, Carbohydrate Structure, and Self-association From Atomistic and Coarse-grained Simulations.” 2015. Web. 17 Jan 2021.

Vancouver:

Fortunato ME. Immunoglobulin G: Solution Dynamics, Carbohydrate Structure, and Self-association From Atomistic and Coarse-grained Simulations. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Jan 17]. Available from: https://submit-etda.libraries.psu.edu/catalog/24261.

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

Council of Science Editors:

Fortunato ME. Immunoglobulin G: Solution Dynamics, Carbohydrate Structure, and Self-association From Atomistic and Coarse-grained Simulations. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/24261

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

Penn State University

19. Stanik, John Andrew. Efficient simulation of protein surface adsorption using Dissipative Particle Dynamics with specular chain reflection.

Degree: 2015, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/27480

► Understanding interactions within complex biological systems is essential to study protein function and transport, and to enable design of biocompatible devices. Studying such complex systems… (more)

▼ Understanding interactions within complex biological systems is essential to study protein function and transport, and to enable design of biocompatible devices. Studying such complex systems through experiment encounters many challenges, including availability and resolution of experimental data, and control over system parameters to be studied. Computer models are frequently employed to explore such systems. Many biological systems of interest, such as protein surface adsorption, cannot be effectively simulated at the atomistic level. In order to simulate these large systems for the durations required for the desired behavior to evolve, atomistic structure is often represented approximately by “coarse-grain” techniques. Dissipative particle dynamics is one simulation technique which makes large size- and time-scales accessible. Current DPD simulations typically represent two surfaces for adsorption, even when the second surface merely serves to bound the opposite one end of the simulation box. To eliminate the computational demand of such a redundant system, here we use a specular reflecting boundary condition as an alternative. This boundary inverts bead Z-velocity at the box ceiling to bounce them back into the simulation. We identify requirements for a successful reflecting boundary. This boundary is validated by comparison with results of a reference system with a second surface and no reflective boundary. Simulation results including surface adsorption, fluid bead density and temperature are used to confirm the equivalence of the results with both boundary methods. Simulation data are evaluated to assess the adsorption behavior of model protein chains of varying geometry onto simulated surfaces of varying hydrophilicity. It is found that such efficient systems with precise parameter control can prove ideal to evaluate a wide range of surface adsorption behavior which may otherwise be impractical to study in detail. Advisors/Committee Members: Coray M Colina, Thesis Advisor/Co-Advisor.

Subjects/Keywords: Simulation; Protein; Adsorption; Dissipative Particle Dynamics; DPD

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Stanik, J. A. (2015). Efficient simulation of protein surface adsorption using Dissipative Particle Dynamics with specular chain reflection. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/27480

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):

Stanik, John Andrew. “Efficient simulation of protein surface adsorption using Dissipative Particle Dynamics with specular chain reflection.” 2015. Thesis, Penn State University. Accessed January 17, 2021. https://submit-etda.libraries.psu.edu/catalog/27480.

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

MLA Handbook (7^th Edition):

Stanik, John Andrew. “Efficient simulation of protein surface adsorption using Dissipative Particle Dynamics with specular chain reflection.” 2015. Web. 17 Jan 2021.

Vancouver:

Stanik JA. Efficient simulation of protein surface adsorption using Dissipative Particle Dynamics with specular chain reflection. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Jan 17]. Available from: https://submit-etda.libraries.psu.edu/catalog/27480.

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

Council of Science Editors:

Stanik JA. Efficient simulation of protein surface adsorption using Dissipative Particle Dynamics with specular chain reflection. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/27480

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

20. Foster, Leigh Suzanne Holmes. The effect of sequence and environment on the structure and dimerization of amyloid precursor protein.

Degree: PhD, Chemistry, 2015, Boston University

URL: http://hdl.handle.net/2144/15180

► Aggregation of amyloid β (Aβ) protein has been linked to the development of Alzheimer's Disease (AD). The genesis of Aβ involves the cleavage Amyloid Precursor… (more)

▼ Aggregation of amyloid β (Aβ) protein has been linked to the development of Alzheimer's Disease (AD). The genesis of Aβ involves the cleavage Amyloid Precursor Protein (APP) by β-secretase, producing the 99-residue C99 peptide, and the subsequent cleavage of C99 by γ-secretase to produce Aβ. A detailed understanding of the γ-cleavage process is essential to our undertsanding of the pathological mechanisms linking the aggregation of Aβ to the development of AD. This work seeks to provide insight into critical aspects of the structure and dynamics of C99, and the particular roles played by (1) C99 amino acid sequence and (2) the lipid composition of the membrane environment. Many studies have focused on the importance of the C99 sequence, including known studies of Familial AD (FAD) mutants as well as engineered mutations. Specific mutations have been found to affect the processing of C99, which has been linked to changes in the structure of C99 and the formation of C99 homodimers. Similarly, changes in the membrane environment, through variation in lipid composition and the presence of cholesterol, have been found to affect C99 structure and positioning within the membrane as well as C99 dimerization. The results of this work extend our understanding of the APP-C99 system and its interaction with the environment. Using a multiscale simulation approach, we find key structural effects of engineered mutations that suggest possible mechanistic insight into the γ-cleavage process. Using C99 congener peptides, we examine the effect of local membrane environment on the dimerization of C99, focusing on the roles of both the transmembrane (TM) region as well as the juxtamembrane (JM) domain. Further studies characterize the role of a FAD mutation, and demonstrate the effect of the mutation on the dimerization of C99 in agreement with experimental findings. Overall, this work leads to critical insight into the role of sequence and membrane on the structure of C99 in a membrane environment, and provides support for the conjecture that the structure of C99 monomer and homodimer are critical to our understanding of the processing of C99, a critical step in the genesis of Aβ peptide and the etiology of Alzheimer's Disease.

Subjects/Keywords: Chemistry; Computational chemistry; Molecular dynamics; Protein structure

11 more images…

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Foster, L. S. H. (2015). The effect of sequence and environment on the structure and dimerization of amyloid precursor protein. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/15180

Chicago Manual of Style (16^th Edition):

Foster, Leigh Suzanne Holmes. “The effect of sequence and environment on the structure and dimerization of amyloid precursor protein.” 2015. Doctoral Dissertation, Boston University. Accessed January 17, 2021. http://hdl.handle.net/2144/15180.

MLA Handbook (7^th Edition):

Foster, Leigh Suzanne Holmes. “The effect of sequence and environment on the structure and dimerization of amyloid precursor protein.” 2015. Web. 17 Jan 2021.

Vancouver:

Foster LSH. The effect of sequence and environment on the structure and dimerization of amyloid precursor protein. [Internet] [Doctoral dissertation]. Boston University; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/2144/15180.

Council of Science Editors:

Foster LSH. The effect of sequence and environment on the structure and dimerization of amyloid precursor protein. [Doctoral Dissertation]. Boston University; 2015. Available from: http://hdl.handle.net/2144/15180

University of Arizona

21. Bellomo, Dante Anthony. Estimating the Rate of FOXO1 Phosphorylation and Dephosphorylation Using Live Cell Imaging .

Degree: 2020, University of Arizona

URL: http://hdl.handle.net/10150/642098

► FoxO1 is a signaling transcription factor regulated by the growth factor/PI3K/AKT pathway. Phosphorylation of FOXO1 by the serine/threonine kinase AKT, sequesters FOXO1 in the cytoplasm… (more)

Subjects/Keywords: AKT; dynamics; FOXO1; nucleus; protein; trafficking

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Bellomo, D. A. (2020). Estimating the Rate of FOXO1 Phosphorylation and Dephosphorylation Using Live Cell Imaging . (Masters Thesis). University of Arizona. Retrieved from http://hdl.handle.net/10150/642098

Chicago Manual of Style (16^th Edition):

Bellomo, Dante Anthony. “Estimating the Rate of FOXO1 Phosphorylation and Dephosphorylation Using Live Cell Imaging .” 2020. Masters Thesis, University of Arizona. Accessed January 17, 2021. http://hdl.handle.net/10150/642098.

MLA Handbook (7^th Edition):

Bellomo, Dante Anthony. “Estimating the Rate of FOXO1 Phosphorylation and Dephosphorylation Using Live Cell Imaging .” 2020. Web. 17 Jan 2021.

Vancouver:

Bellomo DA. Estimating the Rate of FOXO1 Phosphorylation and Dephosphorylation Using Live Cell Imaging . [Internet] [Masters thesis]. University of Arizona; 2020. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10150/642098.

Council of Science Editors:

Bellomo DA. Estimating the Rate of FOXO1 Phosphorylation and Dephosphorylation Using Live Cell Imaging . [Masters Thesis]. University of Arizona; 2020. Available from: http://hdl.handle.net/10150/642098

22. Morriss-Andrews, Herbert Alexander. Coarse-Grained Molecular Dynamics Simulations of Peptide Aggregation on Surfaces.

Degree: 2014, University of California – eScholarship, University of California

URL: http://www.escholarship.org/uc/item/2ms586vt

► Protein aggregation involves self-assembly of normally soluble proteins or peptides into supramolecular structures. This process is particularly important due to its involvement in several amyloid… (more)

▼ Protein aggregation involves self-assembly of normally soluble proteins or peptides into supramolecular structures. This process is particularly important due to its involvement in several amyloid diseases, such as Parkinson's, Alzheimer's, and Type II diabetes. Several fibrillization mechanisms have been proposed, including a condensation-ordering mechanism where ordered fibril structures emerge from disordered oligomers and a dock-lock mechanism where a growing fibril induces attached polypeptides to organize individually into fibril-compatible conformations.We present a series of computational studies using a coarse-grained peptide aggregate model that exhibits a rich diversity of structures: amorphous/disordered aggregates, beta-barrels, multi-layered fibrils, and aggregates of mixed type. Our model has a tunable backbone stiffness that governs the propensity to form fibrils in bulk solution. In this work, we investigate how this beta-sheet propensity couples with the properties of a surface template to influence the mechanism of aggregation. Here, we focus on peptide aggregation in the presence of three templates: a solid surface, the surface of a pre-existing aggregate seed, and a lipid bilayer. Aggregation on solid hydrophilic or hydrophobic surfaces frequently occurs in many experimental setups. We find that the solid surface strongly biases toward the formation of fibrillar aggregates. Peptide-peptide interactions and surface attraction couple cooperatively on a solid surface to influence the binding/aggregation transition. Aggregation and binding occur almost simultaneously since the surface's crystal symmetry enforces a preferred direction of bound fibril growth, thus accelerating the process.Seeding peptides with compatible aggregates removes the nucleation barrier for aggregation. We find that the aggregation mechanism is strongly dependent on the beta-sheet propensity of both the seed and bulk peptides. Additionally, bulk peptides that exhibit polymorphism can have multiple pathways to aggregation depending on which class of aggregate they initially form. We find that a fibrillar seed can induce amorphous-prone peptides into fibrillar structures via a condensation-ordering mechanism, thus sequestering potentially cytotoxic oligomers into a more inert form.We simulate aggregation on lipid bilayers in an effort to approximate the complexity of the cellular milieu. While aggregation in vivo would occur in the presence of membrane surfaces, few simulation studies have been conducted on this combined system due to its computational complexity. We have determined that a membrane surface, like a crystal surface, biases toward fibrillar aggregates. However, membrane undulations disturb multi-layered fibrils into non-planar beta-sheet structures, such as beta-barrels. The presence of fibrils on the membrane also affects its fluid properties, creating a hexagonally packed lipid ordering underneath the fibrils, locally increasing its bending modulus and aligning lipid tilt to the orientation of the peptides. Thus…

Subjects/Keywords: Biophysics; Aggregation; Membranes; Molecular Dynamics; Protein; Simulation

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Morriss-Andrews, H. A. (2014). Coarse-Grained Molecular Dynamics Simulations of Peptide Aggregation on Surfaces. (Thesis). University of California – eScholarship, University of California. Retrieved from http://www.escholarship.org/uc/item/2ms586vt

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):

Morriss-Andrews, Herbert Alexander. “Coarse-Grained Molecular Dynamics Simulations of Peptide Aggregation on Surfaces.” 2014. Thesis, University of California – eScholarship, University of California. Accessed January 17, 2021. http://www.escholarship.org/uc/item/2ms586vt.

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

MLA Handbook (7^th Edition):

Morriss-Andrews, Herbert Alexander. “Coarse-Grained Molecular Dynamics Simulations of Peptide Aggregation on Surfaces.” 2014. Web. 17 Jan 2021.

Vancouver:

Morriss-Andrews HA. Coarse-Grained Molecular Dynamics Simulations of Peptide Aggregation on Surfaces. [Internet] [Thesis]. University of California – eScholarship, University of California; 2014. [cited 2021 Jan 17]. Available from: http://www.escholarship.org/uc/item/2ms586vt.

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

Council of Science Editors:

Morriss-Andrews HA. Coarse-Grained Molecular Dynamics Simulations of Peptide Aggregation on Surfaces. [Thesis]. University of California – eScholarship, University of California; 2014. Available from: http://www.escholarship.org/uc/item/2ms586vt

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

Virginia Tech

23. Kappiyoor, Ravi. Mechanical Properties of Elastomeric Proteins.

Degree: PhD, Engineering Mechanics, 2014, Virginia Tech

URL: http://hdl.handle.net/10919/54563

► When we stretch and contract a rubber band a hundred times, we expect the rubber band to fail. Yet our heart stretches and contracts the… (more)

Subjects/Keywords: Protein elasticity; molecular dynamics; nanoscale material properties

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Kappiyoor, R. (2014). Mechanical Properties of Elastomeric Proteins. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/54563

Chicago Manual of Style (16^th Edition):

Kappiyoor, Ravi. “Mechanical Properties of Elastomeric Proteins.” 2014. Doctoral Dissertation, Virginia Tech. Accessed January 17, 2021. http://hdl.handle.net/10919/54563.

MLA Handbook (7^th Edition):

Kappiyoor, Ravi. “Mechanical Properties of Elastomeric Proteins.” 2014. Web. 17 Jan 2021.

Vancouver:

Kappiyoor R. Mechanical Properties of Elastomeric Proteins. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10919/54563.

Council of Science Editors:

Kappiyoor R. Mechanical Properties of Elastomeric Proteins. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/54563

24. Kabir, Md Adnan. Biomolecular Folding Rates As Understood From Single-Reaction-Coordinate Langevin Dynamics And Kramers’ Theory.

Degree: M.S. in Physics, Physics and Astronomy, 2015, University of Mississippi

URL: https://egrove.olemiss.edu/etd/1114

► Langevin dynamics was used to model the folding and unfolding of simple, hairpin-like biomolecules whose ends are attached to laser-trapped beads, as occurs in optical… (more)

Subjects/Keywords: Biomolecular; Kramers'; Langevin Dynamics; Protein; Physics

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Kabir, M. A. (2015). Biomolecular Folding Rates As Understood From Single-Reaction-Coordinate Langevin Dynamics And Kramers’ Theory. (Thesis). University of Mississippi. Retrieved from https://egrove.olemiss.edu/etd/1114

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):

Kabir, Md Adnan. “Biomolecular Folding Rates As Understood From Single-Reaction-Coordinate Langevin Dynamics And Kramers’ Theory.” 2015. Thesis, University of Mississippi. Accessed January 17, 2021. https://egrove.olemiss.edu/etd/1114.

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

MLA Handbook (7^th Edition):

Kabir, Md Adnan. “Biomolecular Folding Rates As Understood From Single-Reaction-Coordinate Langevin Dynamics And Kramers’ Theory.” 2015. Web. 17 Jan 2021.

Vancouver:

Kabir MA. Biomolecular Folding Rates As Understood From Single-Reaction-Coordinate Langevin Dynamics And Kramers’ Theory. [Internet] [Thesis]. University of Mississippi; 2015. [cited 2021 Jan 17]. Available from: https://egrove.olemiss.edu/etd/1114.

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

Council of Science Editors:

Kabir MA. Biomolecular Folding Rates As Understood From Single-Reaction-Coordinate Langevin Dynamics And Kramers’ Theory. [Thesis]. University of Mississippi; 2015. Available from: https://egrove.olemiss.edu/etd/1114

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

University of Minnesota

25. Li, Geoffrey. On the Role of Conformational Dynamics in Allostery and Cooperativity in Protein Kinase A.

Degree: PhD, Chemistry, 2017, University of Minnesota

URL: http://hdl.handle.net/11299/195388

► Protein kinases are a large class of enzymes that regulate a wide array of vital cellular processes. Their dysregulation has been associated with fatal diseases… (more)

Subjects/Keywords: allostery; conformational dynamics; cooperativity; NMR; protein kinase

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Li, G. (2017). On the Role of Conformational Dynamics in Allostery and Cooperativity in Protein Kinase A. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/195388

Chicago Manual of Style (16^th Edition):

Li, Geoffrey. “On the Role of Conformational Dynamics in Allostery and Cooperativity in Protein Kinase A.” 2017. Doctoral Dissertation, University of Minnesota. Accessed January 17, 2021. http://hdl.handle.net/11299/195388.

MLA Handbook (7^th Edition):

Li, Geoffrey. “On the Role of Conformational Dynamics in Allostery and Cooperativity in Protein Kinase A.” 2017. Web. 17 Jan 2021.

Vancouver:

Li G. On the Role of Conformational Dynamics in Allostery and Cooperativity in Protein Kinase A. [Internet] [Doctoral dissertation]. University of Minnesota; 2017. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/11299/195388.

Council of Science Editors:

Li G. On the Role of Conformational Dynamics in Allostery and Cooperativity in Protein Kinase A. [Doctoral Dissertation]. University of Minnesota; 2017. Available from: http://hdl.handle.net/11299/195388

University of Southern California

26. Lin, Chih-Ying. Molecular dynamics simulation study of initial protein unfolding induced by the photo-responsive surfactants, azoTAB.

Degree: PhD, Chemical Engineering, 2014, University of Southern California

URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/364713/rec/4186

► How proteins fold and unfold has been a great focus for decades. Techniques of molecular dynamics simulations provide the atomic insight of protein folding/unfolding. Proteins… (more)

Subjects/Keywords: molecular dynamics; simulations; protein; surfactants; folding; unfolding

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Lin, C. (2014). Molecular dynamics simulation study of initial protein unfolding induced by the photo-responsive surfactants, azoTAB. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/364713/rec/4186

Chicago Manual of Style (16^th Edition):

Lin, Chih-Ying. “Molecular dynamics simulation study of initial protein unfolding induced by the photo-responsive surfactants, azoTAB.” 2014. Doctoral Dissertation, University of Southern California. Accessed January 17, 2021. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/364713/rec/4186.

MLA Handbook (7^th Edition):

Lin, Chih-Ying. “Molecular dynamics simulation study of initial protein unfolding induced by the photo-responsive surfactants, azoTAB.” 2014. Web. 17 Jan 2021.

Vancouver:

Lin C. Molecular dynamics simulation study of initial protein unfolding induced by the photo-responsive surfactants, azoTAB. [Internet] [Doctoral dissertation]. University of Southern California; 2014. [cited 2021 Jan 17]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/364713/rec/4186.

Council of Science Editors:

Lin C. Molecular dynamics simulation study of initial protein unfolding induced by the photo-responsive surfactants, azoTAB. [Doctoral Dissertation]. University of Southern California; 2014. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/364713/rec/4186

University of Georgia

27. Ford, Michael Garrett. Galectin-1 binding to LacNAc and 3'-O-substituted LacNAc ligands.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/21495

► Galectins are a class of carbohydrate binding proteins, initially characterized by their affinity for galactose terminating ligands, that play important roles in cellular adhesion and… (more)

▼ Galectins are a class of carbohydrate binding proteins, initially characterized by their affinity for galactose terminating ligands, that play important roles in cellular adhesion and development. There are considerable data on the types of saccharides which bind to the galectin-1 dimer, with higher affinity ligands containing the core sequence Gal-ß-(1,4)-GlcNAc or LacNAc. While initially described as binding specifically to galactose-terminating ligands, a number of important 3’-O-substituted structures are found which are physiologically significant. The capping of galactose with 3’-O-SO3 increases affinity, as does polymerization of LacNAc units as seen in polylactosamine structures found in basement membrane glycoproteins. The addition of sialic acid is another especially significant carbohydrate modification regulating the ability of glycans to bind to galectin-1. While glycans containing a Neu5Ac-a-(2,6)- LacNAc capping structure are unable to bind galectin-1, Neu5Ac-a-(2,3)-LacNAc terminated glycans can bind to galectin-1, with an affinity very similar to the LacNAc disaccharide. The competing actions of sialyltransferases can therefore act as a regulator of galectin-1 binding. The modification of lactosamine in N- and O-linked glycans is thought to be the determining switch in the induction of apoptosis by galectin- 1 in developing thymocytes. The clonal selection of immature thymocytes is dependent on this apoptotic process for the production of T-cells capable of discriminating self/nonself antigens. In order to provide a structural framework for the observations on galectin-1 ligand binding, we have utilized an X-ray structure of the galectin-1 LacNAc complex. Structural information on the complexes of the 3’-O-substituted ligands bound to the carbohydrate recognition domain of galectin-1 is obtained from molecular dynamics studies. The resulting molecular trajectories of galectin-1 – ligand complexes are not only able to reproduce geometric features of the X-ray structure, but also predict novel contacts between 3’-O- substituents and protein residues. Predicted binding energies of conformations taken from MD simulations are derived from the contributions to the binding free energy. The effect of 3’-O- modification of LacNAc on binding can also be studied directly, by observing the properties of the protein – ligand complexes in solution NMR spectroscopy. Monitoring chemical shift changes of backbone resonances during ligand titration is an established measure of changes in the local environment of protein residues due to ligand binding, and such experiments require the assignment of protein backbone resonances. In addition to the traditional suite of 3D experiments normally performed to assign a protein, we have undertaken an assignment strategy which incorporates additional angular information, in the form of the residual dipolar coupling. This approach not only assigned many residues in the galectin-1 binding site, but should also serve as a general tool for the assignment of larger proteins.…

Subjects/Keywords: galectin lectin protein carbohyrate NMR molecular dynamics

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Ford, M. G. (2014). Galectin-1 binding to LacNAc and 3'-O-substituted LacNAc ligands. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/21495

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):

Ford, Michael Garrett. “Galectin-1 binding to LacNAc and 3'-O-substituted LacNAc ligands.” 2014. Thesis, University of Georgia. Accessed January 17, 2021. http://hdl.handle.net/10724/21495.

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

MLA Handbook (7^th Edition):

Ford, Michael Garrett. “Galectin-1 binding to LacNAc and 3'-O-substituted LacNAc ligands.” 2014. Web. 17 Jan 2021.

Vancouver:

Ford MG. Galectin-1 binding to LacNAc and 3'-O-substituted LacNAc ligands. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/10724/21495.

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

Council of Science Editors:

Ford MG. Galectin-1 binding to LacNAc and 3'-O-substituted LacNAc ligands. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/21495

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

University of Manchester

28. Stewart, Andrew. Conformational mapping of dynamic protein systems by PELDOR spectroscopy.

Degree: PhD, 2019, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/conformational-mapping-of-dynamic-protein-systems-by-peldor-spectroscopy(9740832a-7eb9-455c-a5fe-e48690faa55d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799373

► Understanding the relationship between protein structure and function remains a large challenge in protein biochemistry. In particular, large multi-domain proteins pose challenges for determining their… (more)

Subjects/Keywords: calmodulin; PELDOR; DEER; protein; dynamics; EPR

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Stewart, A. (2019). Conformational mapping of dynamic protein systems by PELDOR spectroscopy. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/conformational-mapping-of-dynamic-protein-systems-by-peldor-spectroscopy(9740832a-7eb9-455c-a5fe-e48690faa55d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799373

Chicago Manual of Style (16^th Edition):

Stewart, Andrew. “Conformational mapping of dynamic protein systems by PELDOR spectroscopy.” 2019. Doctoral Dissertation, University of Manchester. Accessed January 17, 2021. https://www.research.manchester.ac.uk/portal/en/theses/conformational-mapping-of-dynamic-protein-systems-by-peldor-spectroscopy(9740832a-7eb9-455c-a5fe-e48690faa55d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799373.

MLA Handbook (7^th Edition):

Stewart, Andrew. “Conformational mapping of dynamic protein systems by PELDOR spectroscopy.” 2019. Web. 17 Jan 2021.

Vancouver:

Stewart A. Conformational mapping of dynamic protein systems by PELDOR spectroscopy. [Internet] [Doctoral dissertation]. University of Manchester; 2019. [cited 2021 Jan 17]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/conformational-mapping-of-dynamic-protein-systems-by-peldor-spectroscopy(9740832a-7eb9-455c-a5fe-e48690faa55d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799373.

Council of Science Editors:

Stewart A. Conformational mapping of dynamic protein systems by PELDOR spectroscopy. [Doctoral Dissertation]. University of Manchester; 2019. Available from: https://www.research.manchester.ac.uk/portal/en/theses/conformational-mapping-of-dynamic-protein-systems-by-peldor-spectroscopy(9740832a-7eb9-455c-a5fe-e48690faa55d).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799373

29. Seckler, James Malcolm. The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase.

Degree: PhD, Physiology and Biophysics, 2011, Case Western Reserve University School of Graduate Studies

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1298562809

► Human Immunodeficiency Virus Type 1 Reverse Transcriptase (RT) is the protein in HIV responsible for transcribing viral RNA into double stranded DNA, making it an… (more)

▼ Human Immunodeficiency Virus Type 1 Reverse Transcriptase (RT) is the protein in HIV responsible for transcribing viral RNA into double stranded DNA, making it an essential component in viral infectivity and the most popular target for anti-viral therapies for HIV. Over the years, a plethora of inhibitors for RT have been developed, and many of them are currently approved for clinical use. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI) are small molecules that act as non-competitive, allosteric inhibitors of RT, binding in a binding pocket inside of the polymerase domain of RT and hampering enzymatic activity. Although this is a widely used class of viral inhibitor, the mechanism of inhibition is currently unknown. In addition to this, most current knowledge of RT is concentrated on the heterodimer, while little is known of the monomeric precursors to this structure. In this study we employ HXMS and SAXS to probe the solution structural dynamics and solution structure of RT heterodimer and monomers. We show that the p51 subunit does not form the stable core of the protein. Rather the core consists of the fingers and palm subdomains of both subunits. A β-sheet that forms half of the NNRTI binding site undergoes slow cooperative unfolding, which is slowed by several orders of magnitude upon NNRTI binding. In addition to this, HXMS analysis reveals an allosteric network of regions that spans both subunits of the RT heterodimer. This network is thought to play a vital role in RT inhibition. The structural dynamics and solution structure of RT monomers were determined, revealing that the monomers were structured but more flexible in solution compared to the solution structure of the heterodimer. HXMS revealed that the monomers had nearly identical secondary structure, with the main difference being slow cooperative unfolding in the p66 thumb subdomain. SAXS revealed that both monomers exist in an ensemble of conformation. The polymerase domain of both monomers exists both in an open p66-like conformation, a closed p51-like conformation, and several unique conformations. This research lays the foundation for a novel method of drug screening and discovery. Advisors/Committee Members: Hopfer, Ulrich (Committee Chair), Wintrode, Patrick (Advisor).

Subjects/Keywords: Biophysics; HIV; reverse transcriptase; protein dynamics

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Seckler, J. M. (2011). The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase. (Doctoral Dissertation). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1298562809

Chicago Manual of Style (16^th Edition):

Seckler, James Malcolm. “The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase.” 2011. Doctoral Dissertation, Case Western Reserve University School of Graduate Studies. Accessed January 17, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1298562809.

MLA Handbook (7^th Edition):

Seckler, James Malcolm. “The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase.” 2011. Web. 17 Jan 2021.

Vancouver:

Seckler JM. The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase. [Internet] [Doctoral dissertation]. Case Western Reserve University School of Graduate Studies; 2011. [cited 2021 Jan 17]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1298562809.

Council of Science Editors:

Seckler JM. The Structural Dynamics of Human Immunodeficiency Virus Type I Reverse Transcriptase. [Doctoral Dissertation]. Case Western Reserve University School of Graduate Studies; 2011. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1298562809

University of Texas – Austin

30. Shahmoradi, Amir. Dissecting the relationship between protein structure and sequence evolution.

Degree: PhD, Physics, 2015, University of Texas – Austin

URL: http://hdl.handle.net/2152/31639

► What can protein structure tell us about protein evolutionary dynamics? Despite extensive variety in their native structures, from hyper-thermostable to intrinsically disordered, all proteins share… (more)

▼ What can protein structure tell us about protein evolutionary dynamics? Despite extensive variety in their native structures, from hyper-thermostable to intrinsically disordered, all proteins share a common feature: flexibility and dynamics at different levels of structure. In addition to spatial dynamics, proteins are also highly evolutionary dynamic polymers, exhibiting variability in their amino acid sequences on evolutionary timescales. Significant variations can be observed in the amino acid sequences of the divergent members of a single protein family, while their native conformations and biological functions remain almost conserved among all members of the family. These evolutionary variations can be due to a combination of point mutations, insertions, deletions or sometimes the rearrangement of domains in the protein sequence. In recent years, it has become increasingly evident that the dynamics of proteins in space and time domains – corresponding to structural and evolutionary variations – mutually influence each other at the amino acid level. In particular, it is generally observed that the amino acids in the core of protein are more conserved than the amino acids on the surface. Some site-specific structural quantities have been already identified that are capable of explaining the general patterns of sequence variability in globular proteins. A prominent example is the amino acid exposure to solvent molecules – typically water – which surround proteins in vivo. Furthermore, some partial associations between the local flexibility, packing density and sequence variability can be also observed among globular proteins. There is however no consensus as to which set of structural characteristics play the dominant role in sequence evolution. The strength of sequence – structure correlations also appear to vary widely from one protein to another, with Spearman's correlation strength ρ ∈ [0.1,0.8]. Throughout a series of works summarized in the following chapters, first I explore the wide spectrum of structural determinants of sequence evolution, their interrelationships, and their role in the evolutionary dynamics of protein. I find that amino acid sites that are important for the overall stability of protein structure in general tend to be highly conserved. In other words, any amino acid substitution that results in a significant change of the potential energy landscape and thus the native conformation of protein, is disruptive and hence occurs less frequently on evolutionary timescale. I also find that long-range interactions among individual amino acids play a weak but non-negligible role in site-specific evolution of proteins and their inclusion generally results in better predictions of sequence evolution from protein structure. Then, I present the results from a comprehensive search for the potential biophysical and structural determinants of protein evolution by studying >200 structural and evolutionary characteristics of proteins in a dataset of viral and enzymatic proteins. I discuss the main… Advisors/Committee Members: Mahajan, Swadesh M. (advisor), Wilke, C. (Claus) (advisor), Orbach, Raymond L (committee member), Marder, Michael P (committee member), Gordon, Vernita D (committee member), Press, William H (committee member).

Subjects/Keywords: Biophysics; Evolutionary biology; Protein dynamics; Viral evolution

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Shahmoradi, A. (2015). Dissecting the relationship between protein structure and sequence evolution. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/31639

Chicago Manual of Style (16^th Edition):

Shahmoradi, Amir. “Dissecting the relationship between protein structure and sequence evolution.” 2015. Doctoral Dissertation, University of Texas – Austin. Accessed January 17, 2021. http://hdl.handle.net/2152/31639.

MLA Handbook (7^th Edition):

Shahmoradi, Amir. “Dissecting the relationship between protein structure and sequence evolution.” 2015. Web. 17 Jan 2021.

Vancouver:

Shahmoradi A. Dissecting the relationship between protein structure and sequence evolution. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/2152/31639.

Council of Science Editors:

Shahmoradi A. Dissecting the relationship between protein structure and sequence evolution. [Doctoral Dissertation]. University of Texas – Austin; 2015. Available from: http://hdl.handle.net/2152/31639

Open Access Theses and Dissertations