Simultaneous sampling of multiple transition channels using adaptive paths of collective variables

Abstract

We present a molecular simulation method to simultaneously find multiple transition pathways and their associated free-energy profiles. The scheme extends path-metadynamics (PMD) [G. Díaz Leines and B. Ensing, Phys. Rev. Lett. 109, 020601 (2012)] and multiple-walker PMD [Pérez de Alba Ortíz et al., J. Chem. Phys. 149, 072320 (2018)] with multiple paths and repulsive walkers (multiPMD). We illustrate multiPMD for two C7eq → C7ax paths in Ace–Ala–Nme and six PPII → PPII paths in Ace–(Pro)4–Nme. We also show a scheme to render an interpretable “PathMap,” showing the free energy ridges between paths and the branching and merging of the transition channels. MultiPMD is a flexible and promising method for systems with competing or controversial pathways, which appear in many biomolecular systems, including proteins and nucleic acids.