title: Multiscale enhanced sampling of intrinsically disordered protein conformations.
abstract: In a recently developed multiscale enhanced sampling (MSES) technique, topology-based coarse-grained (CG) models are coupled to atomistic force fields to enhance the sampling of atomistic protein conformations. Here, the MSES protocol is refined by designing more sophisticated Hamiltonian/temperature replica exchange schemes that involve additional parameters in the MSES coupling restraint potential, to more carefully control how conformations are coupled between the atomistic and CG models. A specific focus is to derive an optimal MSES protocol for simulating conformational ensembles of intrinsically disordered proteins (IDPs). The efficacy of the refined protocols, referred to as MSES-soft asymptote (SA), was evaluated using two model peptides with various levels of residual helicities. The results show that MSES-SA generates more reversible helix-coil transitions and leads to improved convergence on various ensemble conformational properties. This study further suggests that more detailed CG models are likely necessary for more effective sampling of local conformational transition of IDPs. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas, 66506.
authors.forename: Kuo Hao
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, Kansas, 66506.
authors.forename: Jianhan
authors.initials: J
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D064267:Intrinsically Disordered Proteins; D010455:Peptides
keywords: intrinsically disordered proteins; molecular dynamics; protein structure; replica exchange