Improvement of protein-compound docking scores by using amino-acid sequence similarities of proteins.
The low accuracy of predicted docking scores is critical at in silico drug screening. In order to improve the accuracy of docking scores, we approximated the protein-compound binding free energy as a linear combination of the raw docking scores of a target compound with many different protein pockets. The coefficients of the linear combination were estimated by the similarities among proteins, simply by using the amino-acid sequence similarities or identities of the proteins. This method was applied to in silico screening of the active compounds of five target proteins, and it increased the hit ratio by approximately four to five times compared to that given only by the raw docking scores in every case. The hit ratio also became robust against differences of target proteins.
Fukunishi
Yoshifumi
Y
Biological Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), 2-41-6, Aomi, Koto-ku, Tokyo 135-0064, Japan. y-fukunishi@aist.go.jp
Nakamura
Haruki
H
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis*; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D030562:Databases, Protein; D015195:Drug Design; D008024:Ligands; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D000596:Amino Acids; D008024:Ligands; D011506:Proteins