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 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.

• Received 23 May 2014

DOI:https://doi.org/10.1103/PhysRevLett.114.098103