THE RATIONAL EVOLUTION OF SCORPION TOXINS

A theoretical method for the rational design of a ''universal'' scorpi on toxin with a wider spectrum of specificity for K+ channels and a mo re stable alpha/beta-folding than in its natural homologues is describ ed. On the basis of the analysis of molecular hydrophobic potentials ( MHP) of the protein spatial structures, structural features for a fami ly of five short scorpion toxins were revealed. The analysis of the ma ps of two-dimensional intramolecular MHP contacts allowed the identifi cation of amino acid residues responsible for the folding of the prote in and/or for the manifestation of its specific function. The theoreti cally predicted structure-function roles of the residues were compared with experimental data on the mutagenesis of charybdotoxin. Based on the results of MHP calculations and with the theory of protein molecul ar evolution used as an additional criterion for the selection of muta tions, the amino acid sequence and the spatial structure of a ''univer sal'' scorpion toxin were determined.