Learning protein-ligand unbinding pathways via single-parameter community detection
arXiv:2402.07103 · doi:10.1021/acs.jctc.4c00250
Abstract
Understanding the dynamics of biomolecular complexes, e.g., of protein-ligand (un)binding, requires the understanding of paths such systems take between metastable states. In MD simulation data, paths are usually not observable per se, but need to be inferred from simulation trajectories. Here we present a novel approach to cluster trajectories based on a community detection algorithm that requires the definition of only a single free parameter. Using the streptavidin-biotin complex as benchmark system and the A\textsubscript{2a} adenosine receptor in complex with the inhibitor ZM241385 as an elaborate application, we demonstrate how such clusters of trajectories correspond to pathways, and how the approach helps in the identification of reaction coordinates for a considered (un)binding process.
This preprint is the unedited version of a manuscript that has been published as peer-reviewed article by J. Chem. Theory Comput. and can be downloaded for private use only. Copyright with the journal, ACS and the authors
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