Enrichments of Ensemble Docking Strategy Based on the Bayesian Model
Abstract MotivationChallenges remained in structure-based drug discovery which include protein flexibility in binding site. Thus, concerning the flexibility of proteins, docking into an ensemble of rigid conformations (ensemble docking) have been proposed with incorporation into protein flexibility with expects that it could provide higher enrichments than rigid single receptor. Here we have developed the ensemble docking strategy by using Bayesian Model algorithms, and this method is validated by three proteins: BTK, JAK and PARP. The Bayesian Model was used to integrate independent docking runs of an ensemble of rigid crystal structures and MD simulations. ResultsThe structure of MD simulations outperforms the crystal structures in separating inhibitors from decoys in BTK and PARP. Further, the results demonstrated that the ensemble docking strategy has better performance than rigid single conformation.