The software package CRASP is designed to detect the pairs of positions
whereat the substitutions are fixed in a coadaptive mode; clusters
of such positions (or coadaptive networks); and integral physico-chemical
characteristics of the proteins that are conserved mainly due to coadaptive
substitutions of their amino acid residues. CRASP has a HTML interface
and is installed with the server of the Laboratory of theoretical
genetics at http://wwwmgs.bionet.nsc.ru/programs/CRASP/. Multiple
alignment of the sequences of a protein family is used as an input
data. Three major problems arise while analyzing coadaptive substitutions:
(1) Taking into account evolutionary dependence of the sequences analyzed;
(2) Taking into account indirect (mediated) correlations; and
(3) The problem of stability of correlation coefficient estimates.
The ways to solve these problems in the CRASP package are discussed.
The approach developed was applied to analysis of protein families
of DNA binding domains of transcription factors as well as families
of protein sequences obtained experimentally by artificial selection
technique. The analysis carried out demonstrates that fixation of
coadaptive substitutions is a common feature of protein families evolution.
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