Cooperativity, Local-Nonlocal Coupling, and Nonnative Interactions: Principles of Protein Folding from Coarse-Grained Models

Summary, in English

Coarse-grained, self-contained polymer models are powerful tools in the study of protein folding. They are also essential to assess predictions from less rigorous theoretical approaches that lack an explicit-chain representation. Here we review advances in coarse-grained modeling of cooperative protein folding, noting in particular that the Levinthal paradox was raised in response to the experimental discovery of two-state-like folding in the late 1960s, rather than to the problem of conformational search per se. Comparisons between theory and experiment indicate a prominent role of desolvation barriers in cooperative folding, which likely emerges generally from a coupling between local conformational preferences and nonlocal packing interactions. Many of these principles have been elucidated by native-centric models, wherein nonnative interactions may be treated perturbatively. We discuss these developments as well as recent applications of coarse-grained chain modeling to knotted proteins and to intrinsically disordered proteins.

• Author: Hue Sun Chan; Zhuqing Zhang; Stefan Wallin; Zhirong Liu
• Department/s: Computational Biology and Biological Physics - Has been reorganised
• Publishing year: 2011
• Language: English
• Pages: 301-326
• Publication/Series: Annual Review of Physical Chemistry
• Volume: 62
• Links: http://dx.doi.org/10.1146/annurev-physchem-032210-103405
• Document type: Journal article review
• Publisher: Annual Reviews
• Topic: Biophysics
• Keywords: native topology; Levinthal paradox; folding funnel; energy landscape; desolvation; enthalpic barrier
• Status: Published
• ISBN/ISSN/Other: ISSN: 1545-1593