Protein threading using PROSPECT: design and evaluation

The computer system PROSPECT for the protein fold recognition using the threading method is described and evaluated in this article. For a given target protein sequence and a template structure, PROSPECT guarantees to find a globally optimal threading alignment between the two. The scoring function for a threading alignment employed in PROSPECT consists of four additive terms: i) a mutation term, ii) a singleton fitness term, iii) a pairwise-contact potential term, and iv) alignment gap penalties. The current version of PROSPECT considers pair contacts only between core (alpha-helix or beta-strand) residues and alignment gaps only in loop regions. PROSPECT finds a globally optimal threading efficiently when pairwise contacts are considered only between residues that are spatially close (7 A or less between the C(beta) atoms in the current implementation). On a test set consisting of 137 pairs of target-template proteins, each pair being from the same superfamily and having sequence identity