A docking interaction study of the effect of critical mutations in ribonuclease a on protein-ligand binding.

Enzymes with ribonucleolytic activity play a pivotal role in gene expression and cellular homeostasis by altering the levels of cellular RNA. Ribonuclease A has been the most well studied of such enzymes whose histidine residues (His(12) and His(119) ) play a crucial role in the catalytic mechanism of the protein. The ligands chosen for this study, 2'CMP and 3'CMP, act as competitive substrate analog inhibitors of this enzyme. Using molecular graphics software freely available for academic use, AutoDock and PyMol, we demonstrate that substitution of either histidine residue by alanine causes marked changes in the distances between these critical residues of the enzyme. The ligands in the docked conformation (particularly on mutation of His(119) to Ala) compensate for the altered free energy and hydrogen bonding abilities in these new protein-ligand complexes.