Revisiting gap locations in amino acid sequence alignments and a proposal for a method to improve them by introducing solvent accessibility

Atsushi Hijikata, Kei Yura, Tosiyuki Noguti, Mitiko Go*

*この研究の対応する著者

研究成果: Article査読

18 被引用数 (Scopus)

抄録

In comparative modeling, the quality of amino acid sequence alignment still constitutes a major bottleneck in the generation of high quality models of protein three-dimensional (3D) structures. Substantial efforts have been made to improve alignment quality by revising the substitution matrix, introducing multiple sequences, replacing dynamic programming with hidden Markov models, and incorporating 3D structure information. Improvements in the gap penalty have not been a major focus, however, following the development of the affine gap penalty and of the secondary structure dependent gap penalty. We revisited the correlation between protein 3D structure and gap location in a large protein 3D structure data set, and found that the frequency of gap locations approximated to an exponential function of the solvent accessibility of the inserted residues. The nonlinearity of the gap frequency as a function of accessibility corresponded well to the relationship between residue mutation pattern and residue accessibility. By introducing this relationship into the gap penalty calculation for pairwise alignment between template and target amino acid sequences, we were able to obtain a sequence alignment much closer to the structural alignment. The quality of the alignments was substantially improved on a pair of sequences with identity in the "twilight zone" between 20 and 40%. The relocation of gaps by our new method made a significant improvement in comparative modeling, exemplified here by the Bacillus subtilis yitF protein. The method was implemented in a computer program, ALAdeGAP (ALignment with Accessibility dependent GAp Penalty), which is available at.

本文言語English
ページ(範囲)1868-1877
ページ数10
ジャーナルProteins: Structure, Function and Bioinformatics
79
6
DOI
出版ステータスPublished - 2011 6月
外部発表はい

ASJC Scopus subject areas

  • 構造生物学
  • 生化学
  • 分子生物学

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