Correlation of docking energies with spectroscopic kinetic assays of potential xanthine oxidase substrates.docVIP

Vol.4, No.1, 22-27 (2013) Journal of Biophysical Chemistry /10.4236/jbpc.2013.41003 Correlation of docking energies with spectroscopic kinetic assays of potential xanthine oxidase substrates Amy L. Stockert , Tarek M. Mahfouz , Brad Petersen , Oluwaseun L. Fakunmoju 1* 1 2 1 1 * 2 Department of Pharmaceutical and Biomedical Sciences, Raabe College of Pharmacy, Ohio Northern University, Ada, USA; Corresponding Author: a-stockert@ Pharmacy Administration, Ohio Health Grant Medical Center, Columbus, USA Received 4 October 2012; revised 12 November 2012; accepted 20 November 2012 ABSTRACT can identify which binding mode is more favorable and the results can be used to find inhibitors for target pro- teins and thus to design new drugs. Therefore, we use Glide (Grid-base Ligand Docking with Energetics) pro- gram to generate ligand poses to search for possible lo- cations of ligand molecules in the active-site region of the receptor. Our goal was to develop a more effective and high throughput method of ranking compounds ac- cording to potential function as inhibitors to the enzyme. We selected bovine xanthine oxidase based on its well characterized mechanism, available structures, and pro- pensity to accept a wide variety of compounds in its ac- tive site. Additionally, the similarities between bovine xanthine oxidase and human xanthine oxidase make the bovine enzyme an appropriate medical target [1-9]. Xanthine oxidase (XO) is an enzyme that converts hypoxanthine to xanthine and xanthine to uric acid, the last two steps in purine metabolism. XO is a molybde- num enzyme, which uses a unique mechanism of sub- strate hydroxylation. Unlike mono-oxygenase systems, the mechanism of molybdenum enzymes contains reduc- tive and oxidat