title: Docking of sulfonamides to carbonic anhydrase II and IV.
abstract: Starting with a known active site of a protein and a database of compounds, one would like to quickly identify a few compounds that "dock" into the active site and obtain "good" binding free energies. The main goal of current automated docking procedures is to predict the "best" substrate-enzyme complex while other programs such as UHBD and DelPhi can be used to compute binding free energies. In this paper, we will focus on the application of docking methods and parameters to study substrate-enzyme interactions of a metalloenzyme system. Specifically, we report on the docking of sulfonamides to carbonic anhydrase II and IV, which are of interest due to their application in glaucoma therapy. Using a standard docking protocol, it is possible to correctly predict not only the orientation of inhibitors to a specific isozyme, but also determine the qualitative affinity for a group of inhibitor for an isozyme.
authors.affiliation: Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania, USA.
authors.forename: E X
authors.initials: EX
authors.lastname: Esposito
authors.forename: K
authors.initials: K
authors.lastname: Baran
authors.forename: K
authors.initials: K
authors.lastname: Kelly
authors.forename: J D
authors.initials: JD
authors.lastname: Madura
mesh_terms: D000465:Algorithms; D002256:Carbonic Anhydrases / Q000737:chemistry*; D003196:Computer Graphics; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D016208:Databases, Factual; D005544:Forecasting; D005901:Glaucoma / Q000188:drug therapy; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry; D008667:Metalloproteins / Q000737:chemistry*; D008956:Models, Chemical; D013379:Substrate Specificity; D013449:Sulfonamides / Q000737:chemistry*; D013678:Technology, Pharmaceutical
chemical_list: D007527:Isoenzymes; D008667:Metalloproteins; D013449:Sulfonamides; D002256:Carbonic Anhydrases