EVALUATION OF THREADING SPECIFICITY AND ACCURACY

Threading experiments with proteins from the globin family provide an indication of the nature of the structural similarity required for suc cessful fold recognition and accurate sequence-structure alignment. Th reading scores are fouled to rise above the noise of false positives w henever roughly 60% of residues from a sequence can be aligned with an alogous sites in the structure of a remote homolog. Fold recognition s pecificity thus appears to be limited by the extent of structural simi larity, regardless of the degree of sequence similarity. Threading ali gnment accuracy is found to depend more critically on the degree of st ructural similarity. Alignments are accurate, placing the majority of residues exactly as in structural alignment, only when superposition r esiduals are less than 2.5 Angstrom. These criteria for successful rec ognition and sequence-structure alignment appear to be consistent with the successes and failures of threading methods in blind structure pr ediction. They also suggest a direct assay for improved threading meth ods: Potentials and alignment models should be tested for their abilit y to detect less extensive structural similarities, and to produce acc urate alignments when superposition residuals for this conserved ''cor e'' fall in the range characteristic of remote homologs. (C) 1996 Wile y-Liss, Inc.