REFINEMENT AND RESCORING THE DOCKING RESULTS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have developed a new methodlogy to refine and rescore the docking results. The docking programs use scoring function to determine the relative binding affinity of ligands and rank order them. These scoring functions are often approximate and empirical in nature. We believe that the large number of false positives seen in the docking results are due to the inadequacy in the docking scoring functions. We have developed a method based on all-atom force field with implicit solvation. Our method is quite robust and very fast. For instance it takes only 45 seconds to refine a ligand. We have applied the method to identify putative substrates for enolase superfamily enzymes and also identify inhibitors against E.coli DHFR receptor.