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Evaluation of threading specificity and accuracy
Author(s) -
Bryant Stephen H.
Publication year - 1996
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(199610)26:2<172::aid-prot7>3.0.co;2-i
Subject(s) - threading (protein sequence) , structural alignment , false positive paradox , similarity (geometry) , structural similarity , pattern recognition (psychology) , sequence alignment , artificial intelligence , superposition principle , sequence (biology) , computer science , protein structure , computational biology , algorithm , biology , mathematics , peptide sequence , genetics , image (mathematics) , mathematical analysis , biochemistry , gene
Threading experiments with proteins from the globin family provide an indication of the nature of the structural similarity required for successful fold recognition and accurate sequence‐structure alignment. Threading scores are found to rise above the noise of false positives whenever roughly 60% of residues from a sequence can be aligned with analogous sites in the structure of a remote homolog. Fold recognition specificity thus appears to be limited by the extent of structural similarity, regardless of the degree of sequence similarity. Threading alignment accuracy is found to depend more critically on the degree of structural similarity. Alignments are accurate, placing the majority of residues exactly as in structural alignment, only when superposition residuals are less than 2.5 Å. These criteria for successful recognition and sequence‐structure alignment appear to be consistent with the successes and failures of threading methods in blind structure prediction. They also suggest a direct assay for improved threading methods: Potentials and alignment models should be tested for their ability to detect less extensive structural similarities, and to produce accurate alignments when superposition residuals for this conserved “core” fall in the range characteristic of remote homologs. © 1996 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.