Pocket v.2: further developments on receptor-based pharmacophore modeling.
A deriving pharmacophore model from the three-dimensional structure of a target protein provides helpful information for analyzing protein-ligand interactions and further improvement of ligand binding affinity. A standalone program, Pocket v.2, has been developed based on the original Pocket module in the de novo drug design program LigBuilder. Pocket v.2 is able to derive a pharmacophore model directly from a given protein-ligand complex structure without human intervention. Key features in the pharmacophore model are automatically reduced to a reasonable number. Pocket v.2 has been applied to several case studies, including cyclin dependent kinase 2, HIV-1 protease, estrogen receptor, and 17beta-hydroxysteroid dehydrogenase. It well reproduced previously published pharmacophore models in all of these cases. One notable feature of Pocket v.2 is that it can tolerate minor conformational changes on the protein side upon binding of different ligands to give a consistent pharmacophore model. For different proteins accommodating the same ligand, Pocket v.2 gives similar pharmacophore models, which opens the possibility to classify proteins with their binding features.
Chen
Jing
J
Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Stable and Unstable Species, College of Chemistry, and Center for Theoretical Biology, Peking University, Beijing 100871, P.R. China.
Lai
Luhua
L
D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry; D000465:Algorithms; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry; D015195:Drug Design; D004345:Drug Industry / Q000379:methods*; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D010741:Phospholipases A / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D011960:Receptors, Estrogen / Q000737:chemistry; D012984:Software
D008024:Ligands; D011960:Receptors, Estrogen; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D051357:Cyclin-Dependent Kinase 2; D010741:Phospholipases A