Journal
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
Volume 84, Issue 2, Pages 232-239Publisher
WILEY
DOI: 10.1002/prot.24968
Keywords
protein folding; protein binding; disease-causing mutations; single amino acid variation; folding free energy; binding free energy
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Funding
- NIH [R01GM093937]
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Single amino acid variations (SAV) occurring in human population result in natural differences between individuals or cause diseases. It is well understood that the molecular effect of SAV can be manifested as changes of the wild type characteristics of the corresponding protein, among which are the protein stability and protein interactions. Typically the effect of SAV on protein stability and interactions was assessed via the changes of the wild type folding and binding free energies. However, in terms of SAV affecting protein functionally and disease susceptibility, one wants to know to what extend the wild type function is perturbed by the SAV. Here it is demonstrated that relative, rather than the absolute, change of the folding and binding free energy serves as a good indicator for SAV association with disease. Using HumVar as a source for disease-causing SAV and experimentally determined free energy changes from ProTherm and SKEMPI databases, correlation coefficients (CC) between the disease index (P-d) and relative folding (P-p(r,f)) and binding (P-p(r,b)) probability indexes, respectively, was achieved. The obtained CCs demonstrated the applicability of the proposed approach and it served as good indicator for SAV association with disease. (C) 2015 Wiley Periodicals, Inc.
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