LPATH: A semi-automated Python tool for clustering molecular pathways

Abstract

AbstractThe pathways by which a molecular process transitions to a target state are highly sought-after as direct views of a transition mechanism. While great strides have been made in the physics-based simulation of such pathways, the analysis of these pathways can be a major challenge due to their diversity and variable lengths. Here we present the LPATH Python tool, which implements a semi-automated method for linguistics-assisted clustering of pathways into distinct classes (or routes). This method involves three steps: 1) discretizing the configurational space into key states, 2) extracting a text-string sequence of key visited states for each pathway, and 3) pairwise matching of pathways based on a text-string similarity score. To circumvent the prohibitive memory requirements of the first step, we have implemented a general two-stage method for clustering conformational states that exploits machine learning. LPATH is primarily designed for use with the WESTPA software for weighted ensemble simulations; however, the tool can also be applied to conventional simulations. As demonstrated for the C7eqto C7axconformational transition of alanine dipeptide, LPATH provides physically reasonable classes of pathways and corresponding probabilities.TOC Graphic