Motivation: It is known that the physico-chemical characteristics of proteins underlying specific folding of the polypeptide chain and the protein function are evolutionary conserved. Detection of such characteristics while analyzing homologous sequences would expand essentially the knowledge on protein function, structure, and evolution. These characteristics are maintained constant, in particular, by co-ordinated substitutions. In this process, the destabilizing effect of a substitution may be compensated by another substitution at a different position within the same protein, making the overall change in this protein characteristic insignificant. Consequently, the patterns of co-ordinated substitutions contain important information on conserved physico-chemical properties of proteins, requiring their investigation and development of the corresponding methods and software for correlation analysis of protein sequences available to a wide range of users.
Results: A software package for analyzing correlated amino acid substitutions at different positions within aligned protein sequences was developed. The approach implies searching for evolutionary conserved physico-chemical characteristics of proteins based on the information on the pairwise correlations of amino acid substitutions at different protein positions. The software was applied to analyze DNA-binding domains of the homeodomain class. As a result, two conservative physico-chemical characteristics preserved due to the co-ordinated substitutions at certain groups of positions in the protein sequence. Possible functional roles of these characteristics are discussed.
Availability: The program package is available at http://wwwmgs.bionet.nsc.ru/programs/CRASP/.