The role of solvent in protein folding in vivo
Abstract/Contents
- Abstract
- How a protein folds from an unstructured heteropolymer into a unique native structure is an important unanswered question in the field of molecular biophysics. In recent years, there have been a number of experiments and computer simulations that have provided insight into the mechanism by which folding occurs. Most of these experiments and simulations measure the dynamics of proteins in infinite dilution. However, bulk solvent is different from the cellular environment in which proteins truly fold. In vivo, protein dynamics occur in the context of the crowded cellular milieu as well as in confined spaces such as the chaperonin cavity, the proteosome, the ribosome exit tunnel, the translocon, etc. When considering these factors it is reasonable to assume that proteins may experience different microenvironments when folding in vivo than in bulk, and these differences may constitute a significant piece of the folding puzzle. Here we show via molecular dynamics simulation, that the presence of solvent when confining a mini- protein affects the probability and mechanism of folding. In a separate study, we use computer simulation to calculate the physical properties of water confined to the ribosome exit tunnel. We find that this solvent is quite different from bulk water, possessing a highly heterogeneous free energy landscape containing extensive water structure, areas of reduced solvent entropy. Finally we show that the foldase activity of GroEL cavity mutants is highly correlated with the hydrophilicy of the inner cavity.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Lucent, Del Michael | |
|---|---|---|
| Associated with | Stanford University, Biophysics Program | |
| Primary advisor | Pande, Vijay | |
| Primary advisor | Kasson, Peter M | |
| Thesis advisor | Pande, Vijay | |
| Thesis advisor | Kasson, Peter M | |
| Thesis advisor | Frydman, Judith | |
| Thesis advisor | Levitt, Michael, 1947- | |
| Advisor | Frydman, Judith | |
| Advisor | Levitt, Michael, 1947- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Del Lucent. |
|---|---|
| Note | Submitted to the Program in Biophysics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2010. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Del Michael Lucent
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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