title: Cooperativity, local-nonlocal coupling, and nonnative interactions: principles of protein folding from coarse-grained models.
abstract: 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.
authors: Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada. chan@arrhenius.med.toronto.edu
authors: Hue Sun
authors: HS
authors: Chan
authors: Zhuqing
authors: Z
authors: Zhang
authors: Stefan
authors: S
authors: Wallin
authors: Zhirong
authors: Z
authors: Liu
mesh_terms: D003198:Computer Simulation; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D011506:Proteins