A program that generates amino acid sequences that are compatible with the Greek key protein motif is presented. Using statistical data derived from the structures of molecules from the protein databank, the novel algorithm generates amino acid sequences compatible with an 8-stranded perfect Greek key jellyroll motif. In this motif, all hydrogen bonds present in the theoretical originating beta-hairpin stay in register as the whole 8-stranded domain folds at once in an anticlockwise swirl. Eight residues are generated per strand and 32 residues per sheet making 64 residues in the antiparallel beta-barrel. The seven loops between beta-strands contain an additional 27 residues. All recognized features of beta-sheets and beta-strands, such as alternating hydrophobic, hydrophilic residues with hydrophobics on the narrow-hydrogen-bond-pair, concave side of the theoretical originating beta-ribbon; sheet twist, strand twist, side chain rotation about the strands; the theories of side chain packing between the sheets; an average 30 degrees rotation between beta-sheets; the theoretical anticomplementary patch residues of each sheet; and the anticomplementary, isotropically stressed hyperbolic parabloid shape of each sheet, are taken into account in the program. The sequences of the loops between strands are designed by turn type and strand twist is considered in the design of the motif's single beta-hairpin turn. Secondary structure parameters and between-strand amino acid pair correlations also figure importantly in the novel algorithm.

The programs described herein function as part of a suite of programs designed for pairwise alignment, multiple alignment, generation of randomized sequences, production of alignment scores and a sorting routine for analysis of the alignments produced. The sequence alignment programs penalize gaps (absences of residues) within regions of protein secondary structure and have the added option of 'fingerprinting' structurally or functionally important protein-residues. The multiple alignment program is based upon the sequence alignment method of Needleman and Wunsch and the multiple alignment extension of Barton and Sternberg. Our application includes the feature of optionally weighting active site, monomer--monomer, ligand contact or other important template residues to bias the alignment toward matching these residues. A sum-score for the alignments is introduced, which is independent of gap penalties. This score more adequately reflects the character of the alignments for a given scoring matrix than the gap-penalty-dependent total score described previously in the literature. In addition, individual amino acid similarity scores at each residue position in the alignments are printed with the alignment output to enable immediate quantitative assessment of homology at key sections of the aligned chains.