Development of methodology for high throughput free energy calculations in drug design applications. (2009–2011)
The accurate estimation of binding affinity of a ligand to the protein remains a major challenge in drug discovery. We will develop medium to high throughput single-point free energy calculation methods for drug design applications. The method will be validated against GP (Glycogen phosphorylase, an anti-diabetic target) and PNMT (phenylethanolamine N-methyltransferase, a CNS target) datatsets. The outcomes of this project will be: (a) understanding of the GP-inhibitor binding thermodynamics and insights into anti-diabetic drug design; (b) identification of fragment hits for subsequent lead optimization for PNMT; and (c) a virtual screening protocol for fragment-based drug design.