Consistent interpretation of molecular simulation kinetics using Markov state models biased with external information

Abstract

Molecular simulations can provide microscopic insight into the physical and chemical driving forces of complex molecular processes. Despite continued advancement of simulation methodology, model errors may lead to inconsistencies between simulated and reference (e.g., from experiments or higher-level simulations) observables. To bound the microscopic information generated by computer simulations within reference measurements, we propose a method that reweights the microscopic transitions of the system to improve consistency with a set of coarse kinetic observables. The method employs the well-developed Markov state modeling framework to efficiently link microscopic dynamics with long-time scale constraints, thereby consistently addressing a wide range of time scales. To emphasize the robustness of the method, we consider two distinct coarse-grained models with significant kinetic inconsistencies. When applied to the simulated conformational dynamics of small peptides, the reweighting procedure systematically improves the time scale separation of the slowest processes. Additionally, constraining the forward and backward rates between metastable states leads to slight improvement of their relative stabilities and, thus, refined equilibrium properties of the resulting model. Finally, we find that difficulties in simultaneously describing both the simulated data and the provided constraints can help identify specific limitations of the underlying simulation approach.

References in corpus (1)

• Consistent interpretation of molecular simulation kinetics using Markov state models biased with external information

Cited by in corpus (9)

• Consistent interpretation of molecular simulation kinetics using Markov state models biased with external information
• Accurate structure-based coarse-graining leads to consistent barrier-crossing dynamics
• Concurrent parametrization against static and kinetic information leads to more robust coarse-grained force fields
• Dynamical properties across different coarse-grained models for ionic liquids
• Coarse-grained conformational surface hopping: Methodology and transferability
• Non-equilibrium Markov state modeling of periodically driven biomolecules
• Modeling of biomolecular machines in non-equilibrium steady states
• Microscopic reweighting for non-equilibrium steady states dynamics
• Reweighting non-equilibrium steady-state dynamics along collective variables