Molecular kinetics as hybrid switching diffusions: a general framework for MSM/RD simulation | 14th of January 2021
Mauricio del Razo, DIEP
A novel approach to simulate simple protein-ligand systems at large time- and length-scales is to couple Markov state models (MSMs) of molecular kinetics with particle-based reaction-diffusion (PBRD) simulations; this approach is named MSM/RD. Current formulations of MSM/RD lack an underlying mathematical framework; they are limited to protein-ligand systems, where the ligand orientation and conformation switching are not taken into account; and they lack multi-particle extensions. In this work, we develop a general MSM/RD framework by coarse-graining molecular dynamics into hybrid switching diffusion processes, a class of stochastic process that integrates continuous dynamics and discrete events into the same process. This framework overcomes all the previous difficulties. We further implement and verify it for two toy models of protein-protein interaction and one multiparticle implementation to model the formation of pentameric ring molecules.