Computational Docking Experiments to Find a Ligand that Will Bind to Xanthine Oxidase

Abstract

This project was to seek a uric acid derivative compound that will be able to bind XOD with high affinity, which could possibly be used as an inhibitor to the XOD activity. A computer was used to design several compounds and the program Autodock Vina was used to perform docking of those compounds to see if they can bind XOD. The uric acid structure contains a six-membered and a five-membered rings fused together with three carbonyl groups on the periphery. We sequentially replaced each peripheral carbonyl group by a sulfur atom (a less polar atom), followed by an aldehyde and a carboxylic acid groups (more polar groups) to obtain different derivatives of uric acid. The values of affinity energies for the three derivatives with all three peripheral carbonyls were replaced by either three sulfur atoms, three aldehydes or three carboxylic acids are -3.6 kcal/mol, -1.2 kcal/mol and -0.70 kcal/mol, respectively. The results obtained showed that the sulfur derivative (#2#6#8) had higher affinity than the other ones. However, the carboxylic acid derivatives (most polar group) generally should have higher affinity than the aldehydes and sulfur derivatives because sulfur atoms usually are not as polar as oxygen atoms.