Variation of protein binding cavity volume and ligand volume in protein-ligand complexes.

We have systematically analyzed the variation of protein binding cavity volume of 200 protein-ligand complexes belonging to eight protein families. Wide variation in protein binding cavity volume for the same protein is observed on binding different ligands. Analysis of individual protein families shows high correlation between atom-atom interactions in binding site and ligand volume. This study implies the significance of protein flexibility in docking small molecule inhibitors on the basis of protein binding cavity volume with respect to ligand volume.