气候变化领域集成服务门户(CCPortal): A method of incorporating rate constants as kinetic constraints in molecular dynamics simulations

CCPortal

DOI	10.1073/pnas.2012423118
	A method of incorporating rate constants as kinetic constraints in molecular dynamics simulations
	Faidon Brotzakis Z.; Vendruscolo M.; Bolhuis P.G.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	From the point of view of statistical mechanics, a full characterization of a molecular system requires an accurate determination of its possible states, their populations, and the respective interconversion rates. Toward this goal, well-established methods increase the accuracy of molecular dynamics simulations by incorporating experimental information about states using structural restraints and about populations using thermodynamics restraints. However, it is still unclear how to include experimental knowledge about interconversion rates. Here, we introduce a method of imposing known rate constants as constraints in molecular dynamics simulations, which is based on a combination of the maximum-entropy and maximum-caliber principles. Starting from an existing ensemble of trajectories, obtained from either molecular dynamics or enhanced trajectory sampling, this method provides a minimally perturbed path distribution consistent with the kinetic constraints, as well as modified free energy and committor landscapes. We illustrate the application of the method to a series of model systems, including all-atom molecular simulations of protein folding. Our results show that by combining experimental rate constants and molecular dynamics simulations, this approach enables the determination of transition states, reaction mechanisms, and free energies. We anticipate that this method will extend the applicability of molecular simulations to kinetic studies in structural biology and that it will assist the development of force fields to reproduce kinetic and thermodynamic observables. Furthermore, this approach is generally applicable to a wide range of systems in biology, physics, chemistry, and material science. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Biomolecular simulation; Kinetics; MaxCal; Transition path sampling
语种	英语
scopus关键词	article; conformational transition; kinetics; maximum entropy model; molecular dynamics; physics; protein folding; rate constant; reaction analysis
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181067
作者单位	Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, United Kingdom; Van't Hoff Institute for Molecular Sciences, University of Amsterdam, Amsterdam, 1090 GD, Netherlands
推荐引用方式 GB/T 7714	Faidon Brotzakis Z.,Vendruscolo M.,Bolhuis P.G.. A method of incorporating rate constants as kinetic constraints in molecular dynamics simulations[J],2021,118(2).
APA	Faidon Brotzakis Z.,Vendruscolo M.,&Bolhuis P.G..(2021).A method of incorporating rate constants as kinetic constraints in molecular dynamics simulations.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Faidon Brotzakis Z.,et al."A method of incorporating rate constants as kinetic constraints in molecular dynamics simulations".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).