title: Computer Simulations of Intrinsically Disordered Proteins.
abstract: The investigation of intrinsically disordered proteins (IDPs) is a new frontier in structural and molecular biology that requires a new paradigm to connect structural disorder to function. Molecular dynamics simulations and statistical thermodynamics potentially offer ideal tools for atomic-level characterizations and thermodynamic descriptions of this fascinating class of proteins that will complement experimental studies. However, IDPs display sensitivity to inaccuracies in the underlying molecular mechanics force fields. Thus, achieving an accurate structural characterization of IDPs via simulations is a challenge. It is also daunting to perform a configuration-space integration over heterogeneous structural ensembles sampled by IDPs to extract, in particular, protein configurational entropy. In this review, we summarize recent efforts devoted to the development of force fields and the critical evaluations of their performance when applied to IDPs. We also survey recent advances in computational methods for protein configurational entropy that aim to provide a thermodynamic link between structural disorder and protein activity.
authors.affiliation: Department of Chemistry, Sookmyung Women's University, Yongsan-Ku, Seoul 04310, Korea; email: sihyun@sookmyung.ac.kr.
authors.forename: Song-Ho
authors.initials: SH
authors.lastname: Chong
authors.affiliation: Department of Chemistry, Sookmyung Women's University, Yongsan-Ku, Seoul 04310, Korea; email: sihyun@sookmyung.ac.kr.
authors.forename: Prathit
authors.initials: P
authors.lastname: Chatterjee
authors.affiliation: Department of Chemistry, Sookmyung Women's University, Yongsan-Ku, Seoul 04310, Korea; email: sihyun@sookmyung.ac.kr.
authors.forename: Sihyun
authors.initials: S
authors.lastname: Ham
mesh_terms: D000818:Animals; D019277:Entropy; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D064267:Intrinsically Disordered Proteins; D014867:Water
keywords: configurational entropy; correlation entropy; force field; molecular dynamics; statistical thermodynamics