A relation between the principal axes of inertia and ligand binding

The principal axes of inertia are eigenvectors that can be calculated for any rigid body. We report studies of the position of the principal axes in crystallographically solved protein molecules. We find with high frequency that at least one principal axis penetrates the surface of the respective protein in a region used for ligand binding. In antibody variable regions, an axis goes through the third hypervariable loop of the heavy chain. In major histocompatibility complex proteins, an axis goes through the peptide-binding groove. In protein–protein heterodimers, a principal axis of one subunit will often penetrate the interface formed with the other subunit. In many of these protein–protein complexes, the axis specifically intersects residues known to be critical for molecular recognition.