Evaluating docked complexes with the HINT exponential function and empirical atomic hydrophobicities.
Methods that predict geometries of ligands binding to receptor molecules can facilitate ligand discovery and yield information on the factors governing complementarity. Here, the use of atomic hydrophobicities in evaluating binding modes has been examined with four ligand-receptor complexes of known structure. In each system, hundreds of hypothetical binding orientations were generated with DOCK and evaluated using the HINT (Hydropathic INTeractions) exponential function and atomic hydrophobic constants. In three of the four systems, the experimental binding mode received the best HINT score; in the fourth system, the experimental binding mode scored only slightly lower than a similar, apparently reasonable orientation. The HINT function may be generally useful as a scoring method in molecular docking.
Meng
E C
EC
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143-0446.
Kuntz
I D
ID
Abraham
D J
DJ
Kellogg
G E
GE
D001665:Binding Sites; D002268:Carboxypeptidases / Q000737:chemistry; D043422:Carboxypeptidases A; D002352:Carrier Proteins / Q000737:chemistry; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011506:Proteins / Q000737:chemistry*; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D012984:Software; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry
D002352:Carrier Proteins; D008024:Ligands; D011506:Proteins; D013762:Tetrahydrofolate Dehydrogenase; D012259:Ribonuclease, Pancreatic; D002268:Carboxypeptidases; D043422:Carboxypeptidases A