ABSTRACT
Structure-based virtual screening (VS) is often time-intensive. To be predictive, docking of small molecules to a target structure requires adequate orientational and conformational sampling as well as accurate scoring within the target binding site. Our pharmacophore-based docking method, PhDock, whereby conformers of the same or different molecules sharing a common pharmacophore are overlaid into ensembles and simultaneously docked using their largest three-dimensional (3D) pharmacophore, allows for efficient sampling of the ligand conformations and orientations in the target structure. Theoretical pharmacophore points, which represent hot spots in the target binding site, more preferentially orient the candidate ligands in productive modes. The combination of simultaneously orienting all the ligands within an ensemble combined with the more efficient sampling dramatically improves search times.
