clusttraj: A Solvent-Informed Clustering Tool for Molecular Modeling (2504.14978v3)

Abstract: Clustering techniques are consolidated as a powerful strategy for analyzing the extensive data generated from molecular modeling. In particular, some tools have been developed to cluster configurations from classical simulations with a standard focus on individual units, ranging from small molecules to complex proteins. Since the standard approach includes computing the Root Mean Square Deviation (RMSD) of atomic positions, accounting for the permutation between atoms is crucial for optimizing the clustering procedure in the presence of identical molecules. To address this issue, we present the clusttraj program, a solvent-informed clustering package that fixes inflated RMSD values by finding the optimal pairing between configurations. The program combines reordering schemes with the Kabsch algorithm to minimize the RMSD of molecular configurations before running a hierarchical clustering protocol. By considering evaluation metrics, one can determine the ideal threshold in an automated fashion and compare the different linkage schemes available. The program capabilities are exemplified by considering solute-solvent systems ranging from pure water clusters to a solvated protein or a small solute in different solvents. As a result, we investigate the dependence on different parameters, such as the system size and reordering method, and also the representativeness of the cluster medoids for the characterization of optical properties. clusttraj is implemented as a Python library and can be employed to cluster generic ensembles of molecular configurations that go beyond solute-solvent systems.