Far-from-equilibrium phenomena in protein dynamics
Abstract/Contents
- Abstract
- The diverse physical principles that govern living things conform to one common precept: all biological processes operate, to some extent, out-of equilibrium. As our understanding of biological pathways advances at the nanoscale, theoretical and simulation techniques that function under non-equilibrium conditions will play an important role in elucidating the working environment of the cell. In this research, large-scale molecular dynamics simulations, discrete dynamical network models, and sophisticated non-equilibrium theories are synthesized to study glassy and dissipative processes facilitated by protein molecules. Leveraging atomistic molecular dynamics data derived from the Folding@home distributed computing project, a number of detailed biophysical systems are examined. I first describe glassy solvent structures that emerge as functional components of a protein chaperone, and I connect such observations to the theory of disordered systems. By coupling Folding@home data, Markov state models of biomolecular dynamics, and the theory of large deviations, I go on to characterize [beta] sheet-rich, amyloid-like misfolded states that appear on protein folding landscapes; I explore the relationship between these misfolded states and so-called dynamical glass transitions. Applying theory related to the Crooks fluctuation theorem, I next explicate the dissipative dynamics in detailed models of signaling proteins, and I illustrate how the input of external energy harmonizes with equilibrium fluctuations to yield functional signaling components. Lastly, I discuss methods by which protein landscapes can be sampled in an adaptive fashion and means for recovering equilibrium kinetics from biased, non-equilibrium simulation data.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Weber, Jeffrey Kurt |
|---|---|
| Associated with | Stanford University, Department of Chemistry. |
| Primary advisor | Pande, Vijay |
| Thesis advisor | Pande, Vijay |
| Thesis advisor | Markland, Thomas E |
| Thesis advisor | Martinez, Todd J. (Todd Joseph), 1968- |
| Advisor | Markland, Thomas E |
| Advisor | Martinez, Todd J. (Todd Joseph), 1968- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Jeffrey Kurt Weber. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Jeffrey Kurt Weber
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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