Using rigidity analysis to probe mutation-induced structural changes in proteins

Predicting how a single amino acid substitution affects the stability of a protein structure is a fundamental task in macromolecular modeling. It has relevance to drug design and understanding of disease-causing protein variants. We present KINARI-Mutagen, a web server for performing in silico mutation experiments on protein structures from the Protein Data Bank. Our rigidity-based approach permits fast evaluation of the effects of mutations that may not be easy to perform in vitro, because it is not always possible to express a protein with a specific amino acid substitution. In two case studies we use KINARI-Mutagen to identify exposed residues that are known to be conserved, and we show that our prediction in the change in a protein´s stability due to a mutation of an amino acid to glycine can be correlated against experimentally derived stability data. KINARI-Mutagen is available at http://kinari.cs.umass.edu.