A combined molecular docking-based and pharmacophore-based target prediction strategy with a probabilistic fusion method for target ranking.
Herein, a combined molecular docking-based and pharmacophore-based target prediction strategy is presented, in which a probabilistic fusion method is suggested for target ranking. Establishment and validation of the combined strategy are described. A target database, termed TargetDB, was firstly constructed, which contains 1105 drug targets. Based on TargetDB, the molecular docking-based target prediction and pharmacophore-based target prediction protocols were established. A probabilistic fusion method was then developed by constructing probability assignment curves (PACs) against a set of selected targets. Finally the workflow for the combined molecular docking-based and pharmacophore-based target prediction strategy was established. Evaluations of the performance of the combined strategy were carried out against a set of structurally different single-target compounds and a well-known multi-target drug, 4H-tamoxifen, which results showed that the combined strategy consistently outperformed the sole use of docking-based and pharmacophore-based methods. Overall, this investigation provides a possible way for improving the accuracy of in silico target prediction and a method for target ranking.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan 610041, China.
Guo-Bo
GB
Li
Ling-Ling
LL
Yang
Yong
Y
Xu
Wen-Jing
WJ
Wang
Lin-Li
LL
Li
Sheng-Yong
SY
Yang
D000465:Algorithms; D001665:Binding Sites; D016000:Cluster Analysis; D016208:Databases, Factual; D015195:Drug Design; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D021281:Quantitative Structure-Activity Relationship; D013629:Tamoxifen / Q000737:chemistry / Q000378:metabolism
D047628:Estrogen Receptor alpha; D013629:Tamoxifen
A probabilistic fusion method; Drug target prediction; Molecular docking; Pharmacophore