Introduction

Markov State Modeling (MSM) is  used to predict both stationary and kinetic quantities on long timescales using a set of atomistic molecular dynamics simulations that are individually much shorter, thus addressing the well-known sampling problem in molecular dynamics simulation.

The MSM method enables an equilibrium binding model and its kinetic barrier heights to be reconstructed from multiple short off-equilibrium simulations. In any given simulated trajectory, only partial binding/unbinding transitions need to be observed. Trajectories are first geometrically clustered in a pre-defined conformational subspace from which a transition matrix (TM) is derived. Kinetic clustering of the eigenvectors of the TM enables metastable states to be identified and fluxes between them computed from transition path theory.

Computational Tools

Markov State Modeling can be performed using the following software tools: