On the effect of protein conformation diversity in discriminating among neutral and disease related single amino acid substitutions.

ABSTRACT:

Background

Non-synonymous coding SNPs (nsSNPs) that are associated to disease can also be related with alterations in protein stability. Computational methods are available to predict the effect of single amino acid substitutions (SASs) on protein stability based on a single folded structure. However, the native state of a protein is not unique and it is better represented by the ensemble of its conformers in dynamic equilibrium. The maintenance of the ensemble is essential for protein function. In this work we investigated how protein conformational diversity can affect the discrimination of neutral and disease related SASs based on protein stability estimations. For this purpose, we used 119 proteins with 803 associated SASs, 60% of which are disease related. Each protein was ass

SUBMITTER: Juritz E 

PROVIDER: S-EPMC3303731 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature