A Practical Covariance-Based Method for Efficient Detection of Protein-Protein Attractive and Repulsive Interactions in Molecular Dynamics Simulations.

Abstract

Molecular dynamics simulations of large protein-protein complexes require scalable analysis. We present a correlation-based workflow that systematically identifies both attractive (stabilizing) interactions, such as salt bridges, and repulsive (destabilizing) interactions, such as same-charge electrostatic repulsions, across extensive interfaces. By constructing an interprotein covariance matrix, filtering residue pairs by distance, and identifying interactions underlying these correlations, our method focuses computational resources on the most relevant regions of the interface while preserving a high level of detail.