Structural and Energetic Analyses of SNPs in Drug Targets and Implications for Drug Therapy

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.