title: Ligand aligning method for molecular docking: alignment of property-weighted vectors.
abstract: To reduce searching effort in conformational space of ligand docking positions, we propose an algorithm that generates initial binding positions of the ligand in a target protein, based on the property-weighted vector (P-weiV), the three-dimensional orthogonal vector determined by the molecular property of hydration-free energy density. The alignment of individual P-weiVs calculated separately for the ligand and the protein gives the initial orientation of a given ligand conformation relative to an active site; these initial orientations are then ranked by simple energy functions, including solvation. Because we are using three-dimensional orthogonal vectors to be aligned, only four orientations of ligand positions are possible for each ligand conformation, which reduces the search space dramatically. We found that the performance of P-weiV compared favorably to the use of principle moment of inertia (PMI) as implemented in LigandFit when we tested the abilities of the two approaches to correctly predict 205 protein-ligand complex data sets from the PDBBind database. P-weiV correctly predicted the alignment of ligands (within rmsd of 2.5 Å) with 57.6% reliability (118/205) for the top 10 ranked conformations and with 74.1% reliability (152/205) for the top 50 ranked conformations of Catalyst-generated conformers, as compared to 22.9% (47/205) and 31.2% (64/205), respectively, in the case of PMI with the same conformer set.
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Joung
authors.forename: Ky-Youb
authors.initials: KY
authors.lastname: Nam
authors.forename: Kwang-Hwi
authors.initials: KH
authors.lastname: Cho
authors.forename: Kyoung Tai
authors.initials: KT
authors.lastname: No
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D062126:Databases, Chemical; D030562:Databases, Protein; D055808:Drug Discovery; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries