Detection of conserved physico-chemical characteristics of proteins by analyzing clusters of positions with co-ordinated substitutions

Motivation: It is known that the physico-chemical characteristics of protei ns underlying specific folding of the polypeptide chain and the protein fun ction are evolutionary conserved. Detection of such characteristics while a nalyzing homologous sequences would expand essentially the knowledge on pro tein function, structure, and evolution. These characteristics are maintain ed constant, in particular, by co-ordinated substitutions. In this process, the destabilizing effect of a substitution may be compensated by another s ubstitution at a different position within the same protein, making the ove rall change in this protein characteristic insignificant. Consequently, the patterns of co-ordinated substitutions contain important information on co nserved physico-chemical properties of proteins, requiring their investigat ion and development of the corresponding methods and software for correlati on analysis of protein sequences available to a wide range of users. Results: A software package for analyzing correlated amino acid substitutio ns at different positions within aligned protein sequences was developed. T he approach implies searching for evolutionary conserved physico-chemical c haracteristics of proteins based on the information on the pairwise correla tions of amino acid substitutions at different protein positions. The softw are 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 pro tein sequence. Possible functional roles of these characteristics are discu ssed.