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.

• Författare: Hue Sun Chan; Zhuqing Zhang; Stefan Wallin; Zhirong Liu
• Avdelning/ar: Beräkningsbiologi och biologisk fysik - Har omorganiserats
• Publiceringsår: 2011
• Språk: Engelska
• Sidor: 301-326
• Publikation/Tidskrift/Serie: Annual Review of Physical Chemistry
• Volym: 62
• Länkar: http://dx.doi.org/10.1146/annurev-physchem-032210-103405
• Dokumenttyp: Artikel i tidskrift
• Förlag: Annual Reviews
• Ämne: Biophysics
• Nyckelord: native topology; Levinthal paradox; folding funnel; energy landscape; desolvation; enthalpic barrier
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1545-1593