Search for sites containing functionally important substitutions in series of related or mutant proteins
Ivanisenko, V.A.; Eroshkin, A.M.
Molekuliarnaia Biologiia 31(5): 880-887
1997
ISSN/ISBN: 0026-8984 PMID: 9454074 Document Number: 480964
A new method is suggested for search of sites containing functionally important substitutions in sets of related or mutant proteins with known activities or other properties. The method is based on calculating a new structure-activity correlation (determination) coefficient called SADC, from the values of activity variation in groups of proteins with similar site structure. The value of SADC corresponds to the squared multiple correlation coefficient between protein activity and various site characteristics. Five protein families were analyzed: disintegrins, alpha-interferons, luciferases, Kunitz proteinase inhibitors, and M2 proteins of influenza virus A. SADC values were calculated for linear, discrete and spatial sites. Positions were identified where differences in amino acid residues correlated with activities and properties of proteins or with phenotypes of respective organism. The positions found were correlated with known functionally important sites of the proteins or close to them. The new method belongs to a series of quantitative protein analysis methods used in the ProAnalyst program (ftp://ftp.ebi.ac.uk/pub/software/dos/panalyst). It can be used for studying the structure-function interactions in proteins and obtaining proteins with controlled changes in activity.