Studies of Voids in Proteins

Previous studies have shown that the hard-sphere plus stereochemical constraint model with explicit hydrogens can accurately predict the side-chain dihedral angle combinations of residues in protein cores. However, the side chain dihedral angle prediction accuracy decreases as the solvent accessible surface area of residues increases, for example near cavities and voids. We performed an analysis of internal cavities in proteins from a database of high-resolution protein crystal structures. We measured void size statistics and void locations in each protein. We correlate the motion of residues in response to mutations to their proximity to large cavities. We show that residues adjacent to larger cavities undergo increased backbone and side chain motion in response to mutations.