A virtual active compound produced from the negative image of a ligand-binding pocket, and its application to in-silico drug screening.
We developed a new structure-based in-silico screening method using a negative image of a ligand-binding pocket and a multi-protein-compound interaction matrix. Based on the structure of the ligand pocket of the target protein, we designed a negative image, which consists of virtual atoms whose radii are close to those of carbon atoms. The virtual atoms fit the pocket ideally and achieve an optimal Coulomb interaction. A protein-compound docking program calculates the protein-compound interaction matrix for many proteins and many compounds including the negative image, which can be treated as a virtual compound. With specific attention to a vector of docking scores for a single compound with many proteins, we selected a compound whose score vector was similar to that of the negative image as a candidate hit compound. This method was applied to representative target proteins and showed high database enrichment with a relatively quick procedure.
Fukunishi
Yoshifumi
Y
Biological Information Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan. y-fukunishi@jbirc.aist.go.jp
Kubota
Satoru
S
Kanai
Chisato
C
Nakamura
Haruki
H
D001665:Binding Sites; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D030562:Databases, Protein; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D066298:In Vitro Techniques; D008024:Ligands; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D013820:Thermolysin / Q000737:chemistry / Q000378:metabolism; D014584:User-Computer Interface
D008024:Ligands; D008263:Macrophage Migration-Inhibitory Factors; D051546:Cyclooxygenase 2; D013820:Thermolysin