Computational Docking of Caffeine Derivatives and Binding to Xanthine Oxidase

Abstract

Building off previous research on XOD ligand docking, the purpose of this project is to seek a caffeine derivative compound structurally similar to Urate and Allopurinol that would exhibit a similar binding mechanism to XOD with high affinity. These modified caffeine molecules could potentially serve as an alternative drug compounds to Allopurinol, an effective inhibitor for XOD. Standard caffeine structure consists of a six-membered and five-membered ring with two carbonyl and three methyl groups directed externally. Our derived caffeine ligands consisted of aldehyde and carboxylic acid side groups replacing the standard methyl groups. Carboxylic and aldehyde side groups were chosen to promote greater polar interactions within the XOD active site. Computational ligand docking to XOD was performed via the Autodock Vina program and ligand analysis focused on ligand binding affinity in comparison to standard Urate values. Our findings indicate that a standard caffeine molecule exhibits poor binding and low affinity to XOD in comparison to Urate. However, a caffeine derivative with a lone carboxylic acid side group and no methyl groups displays a high affinity value comparable to that of Urate and Allopurinol values.