METAL SEARCH - A COMPUTER-PROGRAM THAT HELPS DESIGN TETRAHEDRAL METAL-BINDING SITES

We describe a computer program (Metal Search) that helps design tetrah edrally coordinated metal binding sites in proteins of known structure . The program takes as input the backbone coordinates of a protein and outputs lists of four residues that might form tetrahedral sites if w ild-type amino acids were replaced by cysteine or histidine. The progr am also outputs the side chain dihedral angles of the amino acids and the coordinates of the predicted metal ion. The only function evaluate d by Metal Search is the ability of side chains to meet simple geometr ic criteria for formation of a tetrahedral site, but these criteria ar e sufficient to produce a manageably small List that can then be evalu ated by other means. The program has been used in the introduction of zinc binding sites in the designed four-helix bundle protein alpha 4 a nd in the B1 domain of streptococcal protein G, and in both cases the tetrahedral coordination of a bound metal ion has been confirmed(1) (K lemba, M., Gardner, K. H., Marine, S., Clarke, N.D., and Regan, L., Na ture: Structural Biology 2:368-373, 1995). (C) 1995 Wiley-Liss, Inc.