Structure-based Binding Analysis of Undecaprenyl Pyrophosphate Phosphatase Inhibitors by Consensus Re-scoring

Abstract

Conventional individual scoring functions does not address the problem of designing accurate scoring functions in improving the performance of molecular docking.  In order to cope with the problem, we used the consensus re-scoring method for docking of undecaprenyl pyrophosphate phosphatase (UPPP) and its inhibitors.  In the case of consensus re-scoring strategy, four scoring functions (HEX, PATCHDOCK, FIREDOCK and GOLD scores) are used to evaluate candidate structures for enzyme-inhibitor complex characterization, the rank-by-score was observed 0.96, 1.00, 1.00 and 0.91 for inhibitor-8 and the Consensus Average Auto-Scaled Score was 0.97 among 10 inhibitors. In this study, we found that the inhibitor-8 have more interactions with UPPP enzyme among ten inhibitors based on least binding energy and highest patch docking score. By incorporating consensus re-scoring method into molecular docking programs, reasonable inhibitor models are obtained more efficiently than those selected by independent individual docking scores. This strategy might also improve the scoring of docking programs and increase the performance of structure-based drug design (SBDD).