Abstract: In this communication, we report the development of a novel quantum mechanics-based scoring function to predict free energy of ligand binding in the zinc metalloenzymes carbonic anhydrase (CA) and carboxypeptidase A (CPA). In particular, the AM1 method is used in conjunction with solvation modeling to predict the relative binding affinities of 18 CA and 5 CPA inhibitors. The effect of metal-ligand charge transfer is also discussed and shown to be different in CPA and CA, providing a further challenge to computing metalloenzyme binding affinities.

Authors: Kaushik Raha and Kenneth M. Merz, Jr.

Reference: J. Am. Chem. Soc. 2004, 126(4), 1020-1021. (see link for full paper).