Variational Scheme to Compute Protein Reaction Pathways using Atomistic Force Fields with Explicit Solvent

TL;DR

This paper presents a variational approximation method for simulating rare conformational transitions in proteins, achieving comparable accuracy to molecular dynamics with significantly reduced computational cost.

Contribution

The authors develop a novel variational scheme that enables efficient simulation of protein folding using atomistic force fields with explicit solvent, outperforming traditional MD in speed.

Findings

Results consistent with MD simulations

Significantly reduced computational cost

Applicable to complex protein folding processes

Abstract

We introduce a variational approximation to the microscopic dynamics of rare conformational transitions of macromolecules. Within this framework it is possible to simulate on a small computer cluster reactions as complex as protein folding, using state of the art all-atom force fields in explicit solvent. We test this method against molecular dynamics (MD) simulations of the folding of an alpha- and a beta-protein performed with the same all-atom force field on the Anton supercomputer. We find that our approach yields results consistent with those of MD simulations, at a computational cost orders of magnitude smaller.