maze: Heterogeneous Ligand Unbinding along Transient Protein Tunnels (1904.03929v2)

Abstract: Recent developments in enhanced sampling methods showed that it is possible to reconstruct ligand unbinding pathways with spatial and temporal resolution inaccessible to experiments. Ideally, such techniques should provide an atomistic definition of possibly many reaction pathways, because crude estimates may lead either to overestimating energy barriers, or inability to sample hidden energy barriers that are not captured by reaction pathway estimates. Here we provide an implementation of a new method [J. Rydzewski & O. Valsson, J. Chem. Phys. {\bf 150}, 221101 (2019)] dedicated entirely to sampling the reaction pathways of the ligand-protein dissociation process. The program, called \texttt{maze}, is implemented as an official module for PLUMED 2, an open source library for enhanced sampling in molecular systems, and comprises algorithms to find multiple heterogeneous reaction pathways of ligand unbinding from proteins during atomistic simulations. The \texttt{maze} module requires only a crystallographic structure to start a simulation, and does not depend on many \textit{ad hoc} parameters. The program is based on enhanced sampling and non-convex optimization methods. To present its applicability and flexibility, we provide several examples of ligand unbinding pathways along transient protein tunnels reconstructed by \texttt{maze} in a model ligand-protein system, and discuss the details of the implementation.