title: Structural and energetic analyses of SNPs in drug targets and implications for drug therapy.
abstract: Mutations in drug targets can alter the therapeutic effects of drugs. Therefore, evaluating the effects of single-nucleotide polymorphisms (SNPs) on drug-target binding is of significant interest. This study focuses on the analysis of the structural and energy properties of SNPs in successful drug targets by using the data derived from HapMap and the Therapeutic Target Database. The results show the following: (i) Drug targets undergo strong purifying selection, and the majority (92.4%) of the SNPs are located far from the drug-binding sites (>12 Å). (ii) For SNPs near the drug-binding pocket (≤12 Å), nearly half of the drugs are weakly affected by the SNPs, and only a few drugs are significantly affected by the target mutations. These results have direct implications for population-based drug therapy and for chemical treatment of genetic diseases as well.
authors.affiliation: National Key Laboratory of Crop Genetic Improvement, Center for Bioinformatics, College of Life Science and Technology, Huazhong Agricultural University , Wuhan 430070, P.R. China.
authors.forename: Hui-Yong
authors.initials: HY
authors.lastname: Sun
authors.forename: Feng-Qin
authors.initials: FQ
authors.lastname: Ji
authors.forename: Liang-Yu
authors.initials: LY
authors.lastname: Fu
authors.forename: Zhong-Yi
authors.initials: ZY
authors.lastname: Wang
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhang
mesh_terms: D030541:Databases, Genetic; D060148:HapMap Project; D006801:Humans; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D058990:Molecular Targeted Therapy; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D055553:Prescription Drugs / Q000737:chemistry*; D011506:Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics; D012641:Selection, Genetic; D013816:Thermodynamics
chemical_list: D055553:Prescription Drugs; D011506:Proteins