Pharmacophore-based Molecular Docking to Account for Ligand Flexibility

ABSTRACT Rapid computational mining of large 3D molecular databases is central to generat-ing new drug leads. Accurate virtual screening of large 3D molecular databases requires consider-ation of the conformational flexibility of the ligand molecules. Ligand flexibility can be included with-out prohibitively increasing the search time by docking ensembles of precomputed conformers from a conformationally expanded database. A pharma-cophore-based docking method whereby conform-ers of the same or different molecules are overlaid by their largest 3D pharmacophore and simulta-neously docked by partial matches to that pharma-cophore is presented. Themethod is implemented i