Structure-based pharmacophore modeling and virtual screening to identify novel inhibitors for anthrax lethal factor

摘要: Inhibition of anthrax lethal factor (LF) has been reported to be a potent strategy for the treatment anthrax; however, no effective LF inhibitors are currently available. In this study, structure-based pharmacophore model was developed based on co-crystallized structure with active inhibitor GM6001. The best (denoted as SB_Hypo1), consisting two hydrogen bond acceptors, one donor and hydrophobic, further validated using Gunner-Henry score method. well-validated SB_Hypo1 then used 3D-query in virtual screening identify potential hits from NCI database. These were subsequently filtered by ADMET molecular docking experiments, their binding stabilities 10-ns MD simulations. Finally, three identified leads favorable interactions.