Refinement by shifting secondary structure elements improves sequence alignments

Jing Tong, Jimin Pei, Zbyszek Otwinowski, Nick V. Grishin

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Constructing a model of a query protein based on its alignment to a homolog with experimentally determined spatial structure (the template) is still the most reliable approach to structure prediction. Alignment errors are the main bottleneck for homology modeling when the query is distantly related to the template. Alignment methods often misalign secondary structural elements by a few residues. Therefore, better alignment solutions can be found within a limited set of local shifts of secondary structures. We present a refinement method to improve pairwise sequence alignments by evaluating alignment variants generated by local shifts of template-defined secondary structures. Our method SFESA is based on a novel scoring function that combines the profile-based sequence score and the structure score derived from residue contacts in a template. Such a combined score frequently selects a better alignment variant among a set of candidate alignments generated by local shifts and leads to overall increase in alignment accuracy. Evaluation of several benchmarks shows that our refinement method significantly improves alignments made by automatic methods such as PROMALS, HHpred and CNFpred. The web server is available at http://prodata.swmed.edu/sfesa. Proteins 2015; 83:411-427.

Original languageEnglish (US)
Pages (from-to)411-427
Number of pages17
JournalProteins: Structure, Function and Bioinformatics
Volume83
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

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Keywords

  • Alignment improvement
  • Alignment refinement
  • Contact energy
  • Local secondary structure shifting
  • Pairwise alignment

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Molecular Biology

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