Pharmacophore-based molecular docking to account for ligand flexibility.
Rapid computational mining of large 3D molecular databases is central to generating new drug leads. Accurate virtual screening of large 3D molecular databases requires consideration of the conformational flexibility of the ligand molecules. Ligand flexibility can be included without prohibitively increasing the search time by docking ensembles of precomputed conformers from a conformationally expanded database. A pharmacophore-based docking method whereby conformers of the same or different molecules are overlaid by their largest 3D pharmacophore and simultaneously docked by partial matches to that pharmacophore is presented. The method is implemented in DOCK 4.0.
Joseph-McCarthy
Diane
D
Wyeth Research, Biological Chemistry Department, Cambridge, Massachusetts 02140, USA. djoseph@wyeth.com
Thomas
Bert E
BE
Belmarsh
Michael
M
Moustakas
Demetri
D
Alvarez
Juan C
JC
D000465:Algorithms; D001665:Binding Sites; D001667:Binding, Competitive; D030562:Databases, Protein; D015195:Drug Design; D016333:HIV Protease / Q000737:chemistry; D008024:Ligands; D008727:Methotrexate / Q000737:chemistry; D008782:Methylurea Compounds / Q000737:chemistry; D008958:Models, Molecular; D009249:NADP / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry
C097457:A 79285; D008024:Ligands; D008782:Methylurea Compounds; D011506:Proteins; D011725:Pyridines; D009249:NADP; D013762:Tetrahydrofolate Dehydrogenase; D016333:HIV Protease; D008727:Methotrexate