title: A quantum mechanics-based scoring function: study of zinc ion-mediated ligand binding.
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.affiliation: 152 Davey Laboratory, Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802-6300, USA.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Raha
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Merz
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000737:chemistry*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D002412:Cations; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007700:Kinetics; D008024:Ligands; D008667:Metalloproteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011789:Quantum Theory; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002412:Cations; D008024:Ligands; D008667:Metalloproteins; D011480:Protease Inhibitors; D002268:Carboxypeptidases; D002256:Carbonic Anhydrases; D015032:Zinc