Refinement by shifting secondary structure elements improves sequence alignments

Proteins. 2015 Mar;83(3):411-27. doi: 10.1002/prot.24746. Epub 2015 Jan 13.

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.

Keywords: alignment improvement; alignment refinement; contact energy; local secondary structure shifting; pairwise alignment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Databases, Protein
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Proteins / chemistry*
  • Proteins / metabolism*
  • Proteomics / methods*
  • Sequence Alignment / methods*
  • Thermodynamics

Substances

  • Proteins