SHINE: Deterministic Many-to-Many clustering of Molecular Pathways

Abstract

State-of-the-art molecular dynamics (MD) simulation methods can generate diverse ensembles of pathways for complex biological processes. Analyzing these pathways using statistical mechanics tools demands identifying key states that contribute to both the dynamic and equilibrium properties of the system. This task becomes especially challenging when analyzing multiple MD simulations simultaneously, a common scenario in enhanced sampling techniques like the weighted ensemble strategy. Here, we present a new module of the MDANCE package designed to streamline the analysis of pathway ensembles. This module integrates n-ary similarity, cheminformatics-inspired tools, and hierarchical clustering to improve analysis efficiency. We present the theoretical foundation behind this approach, termed Sampling Hierarchical Intrinsic N-ary Ensembles (SHINE), and demonstrate its application to simulations of alanine dipeptide and adenylate kinase.