BPS2026 – Dynamics of amino acid side-chain packing revealed by Voronoi analysis of simulation trajectories

Conformational motion of proteins is subject to the packing of amino acid side chains with geometric and chemical constraints. Thermal forces and incomplete packing cause proteins to exhibit “breathing” motions that allow for internal flexibility and rearrangement. Understanding packing dynamics therefore provides insights into protein conformational changes, allostery, and response to mechanical load. While Voronoi tessellation is a promising approach to this end, to date, its application to proteins has been mostly limited to static structures. Here, we adopt the Voro++ library to investigate changes in amino acid packing in a protein over time. As a test system, we apply it to all-atom molecular dynamics simulation trajectories of an immunoglobulin domain of titin (PDB 1WAA) at four different temperatures. The Voronoi tessellation includes surface water molecules to properly handle exposed amino acids. We measure per-residue changes in Voronoi volume and the time-dependent reorganization of the faces with neighbors in a Voronoi lattice, and demonstrate their dependence on temperature. This framework can also be applied to the analysis of the dynamics of interfacial residues and water molecules at protein-protein interfaces.