Fig. 1

Overview of the PA/CPA models. a Docking of the compound library into active sites of HCV, DENV, WNV and JEV NS3 proteases using GEMDOCK. For each of the four proteases, top-ranked 3000 hits (based on best calculated interaction energy) are selected to construct interaction profiles. b SimMap analysis of residue-compound interactions leads to Pharmacophore anchor (PA) models of the four NS3 proteases with spatial anchors. c Aligning of PA model anchors yields core anchors shown as the Core pharmacophore anchor (CPA) model. d Validating the PA/CPA model anchors by anchor residue conservation & mutation-activity data analysis and by understanding known inhibitor mechanisms (e) The anchor-based screening carried out for DENV NS3 protease integrates docking by GEMDOCK and the DENV PA model anchors to screen FDA drugs for inhibitor candidates, followed by invitro testing and Structure-anchor-activity relationship (SAAR) studies