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A multiple‐template approach to protein threading
Author(s) -
Peng Jian,
Xu Jinbo
Publication year - 2011
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/prot.23016
Subject(s) - template , threading (protein sequence) , computer science , consistency (knowledge bases) , probabilistic logic , multiple sequence alignment , structural alignment , algorithm , sequence (biology) , protein structure prediction , pairwise comparison , sequence alignment , artificial intelligence , protein structure , peptide sequence , biochemistry , genetics , biology , gene , programming language , physics , chemistry , nuclear magnetic resonance
Most threading methods predict the structure of a protein using only a single template. Due to the increasing number of solved structures, a protein without solved structure is very likely to have more than one similar template structures. Therefore, a natural question to ask is if we can improve modeling accuracy using multiple templates. This article describes a new multiple‐template threading method to answer this question. At the heart of this multiple‐template threading method is a novel probabilistic‐consistency algorithm that can accurately align a single protein sequence simultaneously to multiple templates. Experimental results indicate that our multiple‐template method can improve pairwise sequence‐template alignment accuracy and generate models with better quality than single‐template models even if they are built from the best single templates ( P ‐value <10 −6 ) while many popular multiple sequence/structure alignment tools fail to do so. The underlying reason is that our probabilistic‐consistency algorithm can generate accurate multiple sequence/template alignments. In another word, without an accurate multiple sequence/template alignment, the modeling accuracy cannot be improved by simply using multiple templates to increase alignment coverage. Blindly tested on the CASP9 targets with more than one good template structures, our method outperforms all other CASP9 servers except two (Zhang‐Server and QUARK of the same group). Our probabilistic‐consistency algorithm can possibly be extended to align multiple protein/RNA sequences and structures. Proteins 2011; © 2011 Wiley‐Liss, Inc.