+publisher:"Rutgers University" +contributor:("Levy, Ronald M.")

Rutgers University

1. Dai, Wei. First passage times and relaxation times of unfolded proteins and the funnel model of protein folding.

Degree: PhD, Physics and Astronomy, 2016, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/49952/

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Protein folding has been a challenging puzzle for decades but it is still not fully understood. One important way to gain insights of the mechanism… (more)

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Protein folding has been a challenging puzzle for decades but it is still not fully understood. One important way to gain insights of the mechanism is to study how kinetics in the unfolded state affects protein folding. The answer to this fundamental issue hinges on the time scale to equilibrate the unfolded state and the energy landscape of the unfolded state. We construct Markov state models (MSMs) of several mini-proteins to study the kinetics of their unfolded state ensemble and find that the folding kinetics are two-state even though there are multiple folding pathways with nonuniform barriers, which are the direct consequences of rapid mixing within the unfolded state. Also, we introduce a time integral of a proper correlation function, namely relaxation time, to characterize the time scale of equilibration within the unfolded state. However, the mean first passage times (MFPTs) between different regions of the unfolded state are observed to be orders of magnitude longer than the folding time. This seeming paradox is solved by the derivation of a simple relation that shows the mean first passage time to any state is equal to the relaxation time of that state divided by its equilibrium population. This simple relation explains why MFPTs among unfolded states can be very long but the energy landscape can still be smooth (minimally frustrated). As a matter of fact, when the folding kinetics is two-state, all of the unfolded state relaxation times are faster than the folding time. This result supports the well-established funnel-like energy landscape picture and resolves an apparent contradiction between this model and the recently proposed kinetic hub model of protein folding. Markov state model is a powerful tool but we seek for alternative ways of studying kinetics when MSM does not work very well. For example, diffusion maps of dimensionality reduction and discrete transition-based reweighting analysis method, are very useful in determining a geometrical measure that preserves intrinsic dynamics and in fully utilizing enhanced sampling simulation data.

Advisors/Committee Members: Levy, Ronald M. (chair), Sengupta, Anirvan M. (internal member), Bhanot, Gyan (internal member), Croft, Mark C. (internal member), Tan, Zhiqiang (outside member).

Subjects/Keywords: Protein folding; Markov processes

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APA (6^th Edition):

Dai, W. (2016). First passage times and relaxation times of unfolded proteins and the funnel model of protein folding. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/49952/

Chicago Manual of Style (16^th Edition):

Dai, Wei. “First passage times and relaxation times of unfolded proteins and the funnel model of protein folding.” 2016. Doctoral Dissertation, Rutgers University. Accessed January 23, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/49952/.

MLA Handbook (7^th Edition):

Dai, Wei. “First passage times and relaxation times of unfolded proteins and the funnel model of protein folding.” 2016. Web. 23 Jan 2021.

Vancouver:

Dai W. First passage times and relaxation times of unfolded proteins and the funnel model of protein folding. [Internet] [Doctoral dissertation]. Rutgers University; 2016. [cited 2021 Jan 23]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/49952/.

Council of Science Editors:

Dai W. First passage times and relaxation times of unfolded proteins and the funnel model of protein folding. [Doctoral Dissertation]. Rutgers University; 2016. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/49952/

Rutgers University

2. Flynn, William F., 1988-. Maximum entropy Potts Hamiltonian models of protein fitness and applications to HIV-1 proteins.

Degree: PhD, Physics and Astronomy, 2017, Rutgers University

URL: https://rucore.libraries.rutgers.edu/rutgers-lib/55468/

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Protein evolution is governed by a balance of mutation and selection that act on an ensemble of protein sequence variants. The acquisition of a mutation… (more)

Subjects/Keywords: Maximum entropy method

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

APA (6^th Edition):

Flynn, William F., 1. (2017). Maximum entropy Potts Hamiltonian models of protein fitness and applications to HIV-1 proteins. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/55468/

Chicago Manual of Style (16^th Edition):

Flynn, William F., 1988-. “Maximum entropy Potts Hamiltonian models of protein fitness and applications to HIV-1 proteins.” 2017. Doctoral Dissertation, Rutgers University. Accessed January 23, 2021. https://rucore.libraries.rutgers.edu/rutgers-lib/55468/.

MLA Handbook (7^th Edition):

Flynn, William F., 1988-. “Maximum entropy Potts Hamiltonian models of protein fitness and applications to HIV-1 proteins.” 2017. Web. 23 Jan 2021.

Vancouver:

Flynn, William F. 1. Maximum entropy Potts Hamiltonian models of protein fitness and applications to HIV-1 proteins. [Internet] [Doctoral dissertation]. Rutgers University; 2017. [cited 2021 Jan 23]. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/55468/.

Council of Science Editors:

Flynn, William F. 1. Maximum entropy Potts Hamiltonian models of protein fitness and applications to HIV-1 proteins. [Doctoral Dissertation]. Rutgers University; 2017. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/55468/

3. Narayanan, Chitra, 1981-. Conformational characterization of the intrinsically disordered protein α-Synuclein: a replica exchange molecular dynamics study.

Degree: Biochemistry, 2012, Rutgers University

URL: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000067078

Subjects/Keywords: Protein folding; Amino acids – Metabolism – Disorders; Nervous system – Degeneration

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

APA (6^th Edition):

Narayanan, Chitra, 1. (2012). Conformational characterization of the intrinsically disordered protein α-Synuclein: a replica exchange molecular dynamics study. (Thesis). Rutgers University. Retrieved from http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000067078

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):

Narayanan, Chitra, 1981-. “Conformational characterization of the intrinsically disordered protein α-Synuclein: a replica exchange molecular dynamics study.” 2012. Thesis, Rutgers University. Accessed January 23, 2021. http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000067078.

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

MLA Handbook (7^th Edition):

Narayanan, Chitra, 1981-. “Conformational characterization of the intrinsically disordered protein α-Synuclein: a replica exchange molecular dynamics study.” 2012. Web. 23 Jan 2021.

Vancouver:

Narayanan, Chitra 1. Conformational characterization of the intrinsically disordered protein α-Synuclein: a replica exchange molecular dynamics study. [Internet] [Thesis]. Rutgers University; 2012. [cited 2021 Jan 23]. Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000067078.

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

Council of Science Editors:

Narayanan, Chitra 1. Conformational characterization of the intrinsically disordered protein α-Synuclein: a replica exchange molecular dynamics study. [Thesis]. Rutgers University; 2012. Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000067078

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

4. Paris, Kristina A., 1980-. Modeling receptor reorganization and strain in protein-ligand binding.

Degree: PhD, Chemistry and Chemical Biology, 2011, Rutgers University

URL: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000057657

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The key objectives of computational structure-based drug design include the prediction of the protein-ligand complex binding modes and estimation of the binding affinities. The overall… (more)

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The key objectives of computational structure-based drug design include the prediction of the protein-ligand complex binding modes and estimation of the binding affinities. The overall affinity of a ligand for a receptor can be expressed as a balance between the strength of the interactions of a ligand to any particular binding-competent conformation of the receptor and the probability of occurrence of that conformation in the absence of the ligand. The receptor conformation probability distributions can be described by the free energy landscape of the receptor from which the strain free energy required to move from one conformation to another in the absence of a ligand may be estimated. The availability of large datasets of crystal structures in the PDB can provide information about the locations of free energy basins and their shapes. Here we utilize several methods in an effort to model the strain free energy of several receptors due to binding using the vast structural data publically available in the PDB. Clustering of 99 X-ray structures of HIV-1 reverse transcriptase at the flexible non-nucleoside inhibitor binding pocket elucidates eight discrete clusters, one of which displays a novel bound conformation of the functionally important primer grip. The clustering results served as a guide for replica exchange molecular dynamics simulations that offer a more in-depth look at the potential reorganization of the binding pocket. Clustering of 327 available X-ray structures of HIV-1 protease reveals less discrete variability in the substrate envelope than HIV-1 reverse transcriptase but does reveal some receptor reorganization that may be due to a combination of mutations. A linear response model for incorporation of receptor strain in modern protein-ligand binding affinity estimators is proposed. Receptor-receptor contact counts are employed as estimators for changes in receptor conformation due to binding of different ligands. Overall, the linear model produces apparent reduction in binding energy estimation errors and increases in the rank-order correlation with respect to initial values determined by the commercially available Glide 5.0 XP that does not take into account receptor reorganization. It also offers information as to the type of conformational changes, if any, that may contribute to the receptor reorganization energy. A null hypothesis test is constructed to evaluate the possibility of producing fits by chance alone. Finally, an alternative estimator approach using structurally significant intrareceptor distance descriptors, where there are less possible estimators, shows some promise for several drug targets. The model has the potential to allow for coarse-grained investigation of the conformational and energetic landscapes for binding inhibitors to flexible protein receptors.

Advisors/Committee Members: Paris, Kristina A., 1980- (author), Levy, Ronald M (chair), Arnold, Eddy (internal member), Berman, Helen (internal member), Felts, Anthony K (outside member).

Subjects/Keywords: Protein binding; HIV (Viruses); Reverse transcriptase; Cell receptors

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

APA (6^th Edition):

Paris, Kristina A., 1. (2011). Modeling receptor reorganization and strain in protein-ligand binding. (Doctoral Dissertation). Rutgers University. Retrieved from http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000057657

Chicago Manual of Style (16^th Edition):

Paris, Kristina A., 1980-. “Modeling receptor reorganization and strain in protein-ligand binding.” 2011. Doctoral Dissertation, Rutgers University. Accessed January 23, 2021. http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000057657.

MLA Handbook (7^th Edition):

Paris, Kristina A., 1980-. “Modeling receptor reorganization and strain in protein-ligand binding.” 2011. Web. 23 Jan 2021.

Vancouver:

Paris, Kristina A. 1. Modeling receptor reorganization and strain in protein-ligand binding. [Internet] [Doctoral dissertation]. Rutgers University; 2011. [cited 2021 Jan 23]. Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000057657.

Council of Science Editors:

Paris, Kristina A. 1. Modeling receptor reorganization and strain in protein-ligand binding. [Doctoral Dissertation]. Rutgers University; 2011. Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000057657

5. Hsieh, Daniel, 1984-. Modeling insertion of transmembrane beta-barrels for designing outer membrane proteins.

Degree: Computational Biology and Molecular Biophysics, 2012, Rutgers University

URL: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066761

Subjects/Keywords: Bacterial proteins; Mitochondria – Formation

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Record Details Similar Records Cite « Share

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

APA (6^th Edition):

Hsieh, Daniel, 1. (2012). Modeling insertion of transmembrane beta-barrels for designing outer membrane proteins. (Thesis). Rutgers University. Retrieved from http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066761

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):

Hsieh, Daniel, 1984-. “Modeling insertion of transmembrane beta-barrels for designing outer membrane proteins.” 2012. Thesis, Rutgers University. Accessed January 23, 2021. http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066761.

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

MLA Handbook (7^th Edition):

Hsieh, Daniel, 1984-. “Modeling insertion of transmembrane beta-barrels for designing outer membrane proteins.” 2012. Web. 23 Jan 2021.

Vancouver:

Hsieh, Daniel 1. Modeling insertion of transmembrane beta-barrels for designing outer membrane proteins. [Internet] [Thesis]. Rutgers University; 2012. [cited 2021 Jan 23]. Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066761.

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

Council of Science Editors:

Hsieh, Daniel 1. Modeling insertion of transmembrane beta-barrels for designing outer membrane proteins. [Thesis]. Rutgers University; 2012. Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066761

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

Rutgers University

6. Haq, Omar. Modeling correlated mutations in computational biology using log-linear analysis and graph-theoretic probabilistic inference methods.

Degree: Computational Biology and Molecular Biophysics, 2012, Rutgers University

URL: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066759

Subjects/Keywords: Amino acid sequence; Computational biology; HIV (Viruses)

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

APA (6^th Edition):

Haq, O. (2012). Modeling correlated mutations in computational biology using log-linear analysis and graph-theoretic probabilistic inference methods. (Thesis). Rutgers University. Retrieved from http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066759

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):

Haq, Omar. “Modeling correlated mutations in computational biology using log-linear analysis and graph-theoretic probabilistic inference methods.” 2012. Thesis, Rutgers University. Accessed January 23, 2021. http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066759.

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

MLA Handbook (7^th Edition):

Haq, Omar. “Modeling correlated mutations in computational biology using log-linear analysis and graph-theoretic probabilistic inference methods.” 2012. Web. 23 Jan 2021.

Vancouver:

Haq O. Modeling correlated mutations in computational biology using log-linear analysis and graph-theoretic probabilistic inference methods. [Internet] [Thesis]. Rutgers University; 2012. [cited 2021 Jan 23]. Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066759.

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

Council of Science Editors:

Haq O. Modeling correlated mutations in computational biology using log-linear analysis and graph-theoretic probabilistic inference methods. [Thesis]. Rutgers University; 2012. Available from: http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066759

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

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