pGenTHREADER and pDomTHREADER: new methods for improved protein fold recognition and superfamily discrimination
Open Access
- 7 May 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Bioinformatics
- Vol. 25 (14), 1761-1767
- https://doi.org/10.1093/bioinformatics/btp302
Abstract
Motivation: Generation of structural models and recognition of homologous relationships for unannotated protein sequences are fundamental problems in bioinformatics. Improving the sensitivity and selectivity of methods designed for these two tasks therefore has downstream benefits for many other bioinformatics applications. Results: We describe the latest implementation of the GenTHREADER method for structure prediction on a genomic scale. The method combines profile–profile alignments with secondary-structure specific gap-penalties, classic pair- and solvation potentials using a linear combination optimized with a regression SVM model. We find this combination significantly improves both detection of useful templates and accuracy of sequence-structure alignments relative to other competitive approaches. We further present a second implementation of the protocol designed for the task of discriminating superfamilies from one another. This method, pDomTHREADER, is the first to incorporate both sequence and structural data directly in this task and improves sensitivity and selectivity over the standard version of pGenTHREADER and three other standard methods for remote homology detection. Contact:d.jones@cs.ucl.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.Keywords
This publication has 42 references indexed in Scilit:
- Information theory provides a comprehensive framework for the evaluation of protein structure predictionsProteins-Structure Function and Bioinformatics, 2008
- Exploring the structure and function paradigmCurrent Opinion in Structural Biology, 2008
- SP5: Improving Protein Fold Recognition by Using Torsion Angle Profiles and Profile-Based Gap Penalty ModelPLOS ONE, 2008
- Critical assessment of methods of protein structure prediction—Round VIIProteins-Structure Function and Bioinformatics, 2007
- UniRef: comprehensive and non-redundant UniProt reference clustersBioinformatics, 2007
- SWISS-MODEL: an automated protein homology-modeling serverNucleic Acids Research, 2003
- Protein secondary structure prediction based on position-specific scoring matricesJournal of Molecular Biology, 1999
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997
- Comparative Protein Modelling by Satisfaction of Spatial RestraintsJournal of Molecular Biology, 1993
- Basic local alignment search toolJournal of Molecular Biology, 1990