Analysis of electrostatic and hydrophobic complementarities between chymotrypsin and avian ovomucoid third domains using molecular electrostatic potential: Effect of residue replacements

Electrostatic and hydrophobic complementarities between chymotrypsin and its inhibitor, avian ovomucoid third domains, were evaluated for eight species, which have different amino acid sequences, using molecular electrostatic potential (MEP) and MEP correlation, and the enzyme-inhibitor interaction was analyzed. The changes in the electrostatic and hydrophobic complementarities caused by the amino acid replacements were reflected clearly in the calculated MEP correlation, and it explained the observed binding association constants correctly. The electrostatic complementarity due to arginine at P′3 strongly promotes the binding process of the inhibitor, while the hydrophobic complementarity in the P1 and P′2 positrons also affects the binding process. It was demonstrated that our method is an effective molecular modeling tool in drug design and protein engineering. © 1996 John Wiley & Sons, Inc.