title: Sampling conformational space of intrinsically disordered proteins in explicit solvent: Comparison between well-tempered ensemble approach and solute tempering method.
abstract: Intrinsically disordered proteins (IDPs) are a class of proteins that expected to be largely unstructured under physiological conditions. Due to their heterogeneous nature, experimental characterization of IDP is challenging. Temperature replica exchange molecular dynamics (T-REMD) is a widely used enhanced sampling method to probe structural characteristics of these proteins. However, its application has been hindered due to its tremendous computational cost, especially when simulating large systems in explicit solvent. Two methods, parallel tempering well-tempered ensemble (PT-WTE) and replica exchange with solute tempering (REST), have been proposed to alleviate the computational expense of T-REMD. In this work, we select three different IDP systems to compare the sampling characteristics and efficiencies of the two methods Both the two methods could efficiently sample the conformational space of IDP and yield highly consistent results for all the three IDPs. The efficiencies of the two methods: are compatible, with about 5-6 times better than the plain T-REMD. Besides, the advantages and disadvantages of each method are also discussed. Specially, the PT-WTE method could provide temperature dependent data of the system which could not be achieved by REST, while the REST method could readily be used to a part of the system, which is quite efficient to simulate some biological processes.
authors.affiliation: State Key Laboratory of Multiphase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Mengzhi
authors.initials: M
authors.lastname: Han
authors.affiliation: State Key Laboratory of Multiphase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: xuji@ipe.ac.cn.
authors.forename: Ji
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Multiphase Complex Systems, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address: yren@ipe.ac.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ren
mesh_terms: D000595:Amino Acid Sequence; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D012997:Solvents / Q000737:chemistry*; D013696:Temperature; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry
chemical_list: D064267:Intrinsically Disordered Proteins; D010455:Peptides; D012997:Solvents; D016159:Tumor Suppressor Protein p53
keywords: Free energy surface; Intrinsically disordered protein; Molecular dynamics; Replica exchange with solute tempering; Well-tempered ensemble