Prediction of potential drug targets based on simple sequence properties.
BACKGROUND
During the past decades, research and development in drug discovery have attracted much attention and efforts. However, only 324 drug targets are known for clinical drugs up to now. Identifying potential drug targets is the first step in the process of modern drug discovery for developing novel therapeutic agents. Therefore, the identification and validation of new and effective drug targets are of great value for drug discovery in both academia and pharmaceutical industry. If a protein can be predicted in advance for its potential application as a drug target, the drug discovery process targeting this protein will be greatly speeded up. In the current study, based on the properties of known drug targets, we have developed a sequence-based drug target prediction method for fast identification of novel drug targets.


RESULTS
Based on simple physicochemical properties extracted from protein sequences of known drug targets, several support vector machine models have been constructed in this study. The best model can distinguish currently known drug targets from non drug targets at an accuracy of 84%. Using this model, potential protein drug targets of human origin from Swiss-Prot were predicted, some of which have already attracted much attention as potential drug targets in pharmaceutical research.


CONCLUSIONS
We have developed a drug target prediction method based solely on protein sequence information without the knowledge of family/domain annotation, or the protein 3D structure. This method can be applied in novel drug target identification and validation, as well as genome scale drug target predictions.
Li
Qingliang
Q
Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Structural Chemistry for Stable and Unstable Species, College of Chemistry and Molecular Engineering, Peking University, 100871 Beijing, China. qlli@pku.edu.cn
Lai
Luhua
L
D019295:Computational Biology / Q000379:methods*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D004364:Pharmaceutical Preparations; D011506:Proteins