title: Ligand shape emerges in solvent dipole ordering region at ligand binding site of protein.
abstract: Solvent dipole ordering (SDO), introduced by Higo et al. (Proteins Struct Funct Genet 2000, 40, 193), is an entity that captures an aspect of hydration structure. We have studied SDO in the ligand binding site of two proteins (FK506 binding protein and dihydrofolate reductase) and found that the high SDO regions overlap significantly with the 3D structures of known inhibitors bound to the proteins. Thus, the SDO region might be used to predict the preferred molecular shape of ligands that bind to a protein. Based on this finding, we propose a novel docking procedure using model molecules that mimic the shape of the SDO region. To prove the validity of thisapproach, we performed a redocking experiment for p38 mitogen-activated protein kinase ligands using model molecules for search queries; we succeeded in identifying the binding conformations and binding modes of known inhibitors.
authors: Department of Theoretical Drug Design, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501 Japan. murata@pharm.kyoto-u.ac.jp
authors: Katsumi
authors: K
authors: Murata
authors: Naoya
authors: N
authors: Nagata
authors: Isao
authors: I
authors: Nakanishi
authors: Kazuo
authors: K
authors: Kitaura
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D012997:Solvents / Q000737:chemistry; D022021:Tacrolimus Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D012997:Solvents; D013762:Tetrahydrofolate Dehydrogenase; D022021:Tacrolimus Binding Proteins