title: Large-scale prediction of drug-target interactions using protein sequences and drug topological structures.
abstract: The identification of interactions between drugs and target proteins plays a key role in the process of genomic drug discovery. It is both consuming and costly to determine drug-target interactions by experiments alone. Therefore, there is an urgent need to develop new in silico prediction approaches capable of identifying these potential drug-target interactions in a timely manner. In this article, we aim at extending current structure-activity relationship (SAR) methodology to fulfill such requirements. In some sense, a drug-target interaction can be regarded as an event or property triggered by many influence factors from drugs and target proteins. Thus, each interaction pair can be represented theoretically by using these factors which are based on the structural and physicochemical properties simultaneously from drugs and proteins. To realize this, drug molecules are encoded with MACCS substructure fingerings representing existence of certain functional groups or fragments; and proteins are encoded with some biochemical and physicochemical properties. Four classes of drug-target interaction networks in humans involving enzymes, ion channels, G-protein-coupled receptors (GPCRs) and nuclear receptors, are independently used for establishing predictive models with support vector machines (SVMs). The SVM models gave prediction accuracy of 90.31%, 88.91%, 84.68% and 83.74% for four datasets, respectively. In conclusion, the results demonstrate the ability of our proposed method to predict the drug-target interactions, and show a general compatibility between the new scheme and current SAR methodology. They open the way to a host of new investigations on the diversity analysis and prediction of drug-target interactions.
authors.affiliation: Research Center of Modernization of Traditional Chinese Medicines, Central South University, Changsha, PR China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Cao
authors.forename: Shao
authors.initials: S
authors.lastname: Liu
authors.forename: Qing-Song
authors.initials: QS
authors.lastname: Xu
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Lu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Huang
authors.forename: Qian-Nan
authors.initials: QN
authors.lastname: Hu
authors.forename: Yi-Zeng
authors.initials: YZ
authors.lastname: Liang
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D055808:Drug Discovery; D006801:Humans; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations; D011506:Proteins