CRASP : SOFTWARE PACKAGE FOR ANALYSIS OF PHYSICOCHEMICAL PARAMETERS OF ALIGNED SEQUENCES OF PROTEIN FAMILIES

At present, the data on aligned primary sequences of protein families are being accumulated very rapidly. One of promising approaches to analysis of these data is to study correlations between amino acid substitutions at positions of protein sequences [1-3]. The information obtained could be valuable for revealing the peculiarities of the structure and function of the proteins under study. In relation to this topic, the main goal is to develop publicly available methods and software for correlation analysis of protein sequences. During analysis of co-adaptive substitutions, two important tasks appear. The first is to study correlations of amino acid substitutions at positions of a protein in order to reveal the pairs of residues that are related due to functional interactions (e.g., steric contact). The resulted information could be used for prediction of possible contacts between the residues [4,5]. The second task is to reveal and analyse the conserved integral physico-chemical characteristics of a protein [6,7]. As the examples of these characteristics may serve the total charge of a protein molecule, the volume of its hydrophobic core, hydrophobic moments of alpha helices, etc. The constancy of these characteristics in the course of evolution implies that they are responsible for the key features significant for protein structure and function. Co-adaptive substitutions may be one of possible mechanisms for supporting the constancy of these characteristics, together with invariance of residues at positions of a protein and conserved substitutions of residues to those similar by physico-chemical properties [6]. In the present communication, we introduce the software package CRASP designed for analysis of physicochemical pairwise correlations between amino acid substitutions at positions of aligned sequences of a protein family. In this package, we have realized an approach that is based on revealing of conserved physico-chemical characteristics of a protein obtained on the basis of information about correlations of substitutions of amino acids at the pairwise positions of a protein. The software package is available via the Internet at http://wwwmgs.bionet. nsc.ru/programs/CRASP. By using the software package developed, it is possible to reveal the pairs of protein positions, at which amino acid substitutions occur in a co-adaptive manner; the approach is based on estimation of correlation coefficient between the values of a certain physico-chemical parameter at a pair of positions of multiply aligned proteins. Besides, the package enables the following procedures: to analyze the obtained information on pairwise correlations between substitutions; to reveal both conserved and variable integral physico-chemical characteristics of a protein; to evaluate how conservation (or variability) of revealed characteristics is produced by co-adaptive substitutions of residues. It should be noted that the software package consists of two modules: the program for analysis of correlations of substitutions at the pairs of protein positions and the program for analysis of integral protein characteristics. In principle, the user can address to each of these two modules independently (in particular, in case the physicochemical characteristics is a priori known by a user). The block-scheme of the software package CRASP is shown in Fig. 1.