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.
Keywords: graphical models; large molecular systems; molecular kinetics.