Investigating Rigidity Properties of Protein Cavities

Abstract

Cavities in proteins facilitate a variety of biochemical processes. The shapes and sizes of cavities are factors that contribute to specificity in ligand binding, and docking with other biomolecules. A deep understanding of cavity properties may enable new insights into protein-protein interactions, ligand binding, and structure-based drug design studies. In this work we explore how biological properties such as size and residue membership of protein cavities correlate with the flexibility of the cavity as computed using an efficient graph theoretic rigidity algorithm. We hypothesize that various rigidity properties of protein cavities are dependent on cavity surface area. In this work we enumerate a set of cavity rigidity metrics, and demonstrate their use in characterizing over 120,000 cavities from approximately 2,500 chains. We show that cavity size indeed does correlate with some -- but not all -- cavity rigidity metrics.