Single nucleotide variants in pathological tissues: effect on protein structure and stability

Single nucleotide variants are the most frequent form of human genetic variation occurring, on average, approximately every 1200 base pairs. nsSNPs occur in the DNA coding region and lead to an amino acid change in the protein, missense mutation, that is interesting in medical biology because it may affect protein function and lead to pathogenic phenotypes. Furthermore, nsSNPs have been shown to be related to drugs sensitivity suggesting new therapeutic personalized strategies. In most of the cases the SNPs stability has been considered to be responsible of the mutations impact on the pathological conditions or on the genetic susceptibility to diseases of the individuals. The most common cause of protein loss of function is the destabilization of its native structure and SNPs have been reported to affect protein folding and to produce changes in thermodynamic stability. Experimental studies on thermal and thermodynamic stability of some natural protein variants expressed in cancer tissues revealed a decrease in thermal stability and an increase of protein flexibility. nsSNPs may influence an individual’s susceptibility to disease -or response to drugs- through their impacts on a protein’s structure and hence cause functional changes. The future of SNP analysis greatly lies in the development of personalized medicines that can facilitate the treatment of disorders induced by genomic variations. The knowledge of SNPs will help in understanding pharmacokinetics or pharmacodynamics and how drugs act in individuals with different genetic variants. Diseases with different SNPs may become relevant pharmacogenomic targets for drug therapy.