A relation between the principal axes of inertia and ligand binding

The principal axes of inertia are eigenvectors that can be calculated for a ny rigid body. We report studies of the position of the principal axes in c rystallographically solved protein molecules. We find with high frequency t hat at least one principal axis penetrates the surface of the respective pr otein in a region used for ligand binding. In antibody variable regions, an axis goes through the third hypervariable loop of the heavy chain. In majo r histocompatibility complex proteins, an axis goes through the peptide-bin ding groove. In protein-protein heterodimers, a principal axis of one subun it will often penetrate the interface formed with the other subunit. In man y of these protein-protein complexes, the axis specifically intersects resi dues known to be critical for molecular recognition.