A multiple-template approach to protein threading

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 mo...

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Bibliographic Details
Published in:Proteins, structure, function, and bioinformatics Vol. 79; no. 6; pp. 1930 - 1939
Main Authors: Peng, Jian, Xu, Jinbo
Format: Journal Article
Language:English
Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2011
Wiley Subscription Services, Inc
Subjects:
Algorithms
Databases, Protein
multiple sequence/template alignment
multiple-template threading
probabilistic alignment matrix
probabilistic-consistency algorithm
Protein Conformation
protein modeling
Proteins - chemistry
Sequence Alignment - methods
ISSN:0887-3585, 1097-0134, 1097-0134
Online Access:Get full text
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Summary: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.
Bibliography:National Science Foundation - No. DBI-0960390
National Institute of Health - No. R01GM089753
ArticleID:PROT23016
istex:34CDBF1ACC7058C296BC44D58914A5EF8491743F
ark:/67375/WNG-5GP9W7FQ-6
ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0887-3585
1097-0134
1097-0134
DOI:10.1002/prot.23016