期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：30
页码：15001-15006
DOI：10.1073/pnas.1901692116
出版社：The National Academy of Sciences of the United States of America
摘要：Most current molecular dynamics simulation and analysis methods rely on the idea that the molecular system can be represented by a single global state (e.g., a Markov state in a Markov state model [MSM]). In this approach, molecules can be extensively sampled and analyzed when they only possess a few metastable states, such as small- to medium-sized proteins. However, this approach breaks down in frustrated systems and in large protein assemblies, where the number of global metastable states may grow exponentially with the system size. To address this problem, we here introduce dynamic graphical models (DGMs) that describe molecules as assemblies of coupled subsystems, akin to how spins interact in the Ising model. The change of each subsystem state is only governed by the states of itself and its neighbors. DGMs require fewer parameters than MSMs or other global state models; in particular, we do not need to observe all global system configurations to characterize them. Therefore, DGMs can predict previously unobserved molecular configurations. As a proof of concept, we demonstrate that DGMs can faithfully describe molecular thermodynamics and kinetics and predict previously unobserved metastable states for Ising models and protein simulations.
关键词：graphical models ; molecular kinetics ; large molecular systems
