Abstract
For many decades now, the solution to the protein folding problem has been sought within the thermodynamic hypothesis of Anfinsen. Instead, the work discussed here is concerned with protein folding in vivo and assumes that the solution lies within a generalization of the kinetic, nonequilibrium mechanism first proposed by Levinthal. Accordingly, two different initial conditions, namely, a fully extended and a helical chain, are tested and pathways to the native state are generated via targeted molecular dynamics. The energetic and structural analysis indicates that a helical initial condition is to be preferred over an extended one. These results are set against the broader context of in vitro protein refolding experiments and theories and are found to be in agreement with the recent experimental observations about the influence of the ribosome on the structure of, and on the folding from, nascent chains.
Acknowledgments
Most of these simulations were performed at the Milipeia cluster of the Laboratory for Advanced Computing of the University of Coimbra, Portugal. This research was partially supported by the European Regional Development Fund (ERDF) through the COMPETE-Operational Competitiveness Programme and national funds through Foundation for Science and Technology (FCT), under the project PEst-C/MAR/LA0015/2011.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
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©2014 by De Gruyter
Articles in the same Issue
- Frontmatter
- Reviews
- Attempt at a systemic outlook on aging and carcinogenesis
- A kinetic mechanism for in vivo protein folding
- Production of laser-polarized 3He gas via metastability exchange optical pumping for magnetic resonance imaging
- Operative procedures supported with robotics systems and available endoscope procedures in operative gynecology
- Research Articles
- Virtual patient case: study of a urinary incontinence therapy procedure in a woman
- Involvement of medical experts in legal proceedings: an e-learning approach
Articles in the same Issue
- Frontmatter
- Reviews
- Attempt at a systemic outlook on aging and carcinogenesis
- A kinetic mechanism for in vivo protein folding
- Production of laser-polarized 3He gas via metastability exchange optical pumping for magnetic resonance imaging
- Operative procedures supported with robotics systems and available endoscope procedures in operative gynecology
- Research Articles
- Virtual patient case: study of a urinary incontinence therapy procedure in a woman
- Involvement of medical experts in legal proceedings: an e-learning approach