Pharmacophore based virtual screening, molecular docking studies to design potent heat shock protein 90 inhibitors.

The identification of important chemical features of Heat Shock Protein 90 (HSP90) inhibitors will be helpful to discover the potent candidate to inhibit the HSP90 activity. The best hypothesis from Hip-Hop, Hypo1, one hydrogen bond donor (HBD), two hydrogen bond acceptors (HBA), and two hydrophobic (H) and structure-based hypothesis, SB_Hypo1, one HBA, one HBD and four H features, were generated using Discovery Studio and LigandScout, respectively. Test and decoy sets were used to corroborate the best hypotheses and the validated hypotheses were used to screen the chemical databases. Subsequently, the screened compounds were filtered by applying the rule of five, ADMET and molecular docking. Finally, four compounds were obtained as novel leads to inhibit the HSP90 activity.