Tensor-based Approximation of Molecular Kinetics: Generator Learning, Reaction Coordinates and Incremental Updating

Abstract

We present an approach to analyze long-timescale kinetics of molecular dynamics simulations - meta-stable states and transition timescales - by a tensor-based approximation of the infinitesimal generator. We start from the variational approximation of low-lying generator eigenvalues, and discretize the associated eigenvalue problem using a tensor-product basis. We derive analytical expressions for the resulting tensor operators in tensor train (TT) format, and provide efficient algorithms to solve the corresponding linear problems. We also treat the case of a state-dependent diffusion field, which is relevant when working in reaction coordinates. We show how the number of reaction coordinates can be gradually increased without having to solve the variational problem from scratch. Using MD simulations of fast-folding proteins and TICA coordinates as reaction coordinates, we demonstrate the effectiveness of the proposed method at identifying long-timescale transitions and meta-stable states.