title: Determining Protein Folding Pathway and Associated Energetics through Partitioned Integrated-Tempering-Sampling Simulation.
abstract: Replica exchange molecular dynamics (REMD) and integrated-tempering-sampling (ITS) are two representative enhanced sampling methods which utilize parallel and integrated tempering approaches, respectively. In this work, a partitioned integrated-tempering-sampling (P-ITS) method is proposed which takes advantage of the benefits of both parallel and integrated tempering approaches. Using P-ITS, the folding pathways of a series of proteins with diverse native structures are explored on multidimensional free-energy landscapes, and the associated thermodynamics are evaluated. In comparison to the original form of ITS, P-ITS improves the sampling efficiency and measures the folding/unfolding thermodynamic quantities more consistently with experimental data. In comparison to REMD, P-ITS significantly reduces the requirement of computational resources and meanwhile achieves similar simulation results. The observed structural characterizations of transition and intermediate states of the proteins under study are in good agreement with previous experimental and simulation studies on the same proteins and homologues. Therefore, the P-ITS method has great potential in simulating the structural dynamics of complex biomolecular systems.
authors.affiliation: Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Qiang
authors.identifier: http://orcid.org/0000-0001-6460-3095
authors.initials: Q
authors.lastname: Shao
authors.affiliation: UCB Biopharma SPRL, Chemin du Foriest, 1420 Braine-l'Alleud, Belgium.
authors.forename: Jiye
authors.initials: J
authors.lastname: Shi
authors.affiliation: Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
mesh_terms: D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013696:Temperature
chemical_list: D011506:Proteins