Comparative protein structure modeling by combining multiple templates and optimizing sequence-to-structure alignments

Narcis Fernandez-Fuentes, Brajesh K. Rai, Carlos J. Madrid-Aliste, J. Eduardo Fajardo, András Fiser

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Motivation: Two major bottlenecks in advancing comparative protein structure modeling are the efficient combination of multiple template structures and the generation of a correct input target-template alignment. Results: A novel method, Multiple Mapping Method with Multiple Templates (M4T) is introduced that implements an algorithm to automatically select and combine Multiple Template structures (MT) and an alignment optimization protocol (Multiple Mapping Method, MMM). The MT module of M4T selects and combines multiple template structures through an iterative clustering approach that takes into account the 'unique' contribution of each template, their sequence similarity among themselves and to the target sequence, and their experimental resolution. MMM is a sequence-to-structure alignment method that optimally combines alternatively aligned regions according to their fit in the structural environment of the template structure. The resulting M4T alignment is used as input to a comparative modeling module. The performance of M4T has been benchmarked on CASP6 comparative modeling target sequences and on a larger independent test set, and showed favorable performance to current state of the art methods.

Original languageEnglish (US)
Pages (from-to)2558-2565
Number of pages8
JournalBioinformatics
Volume23
Issue number19
DOIs
StatePublished - Oct 1 2007

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ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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