Beyond the twilight zone : automated prediction of structural properties of proteins by recursive neural networks and remote homology information

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Title: Beyond the twilight zone : automated prediction of structural properties of proteins by recursive neural networks and remote homology information
Authors: Mooney, Catherine
Pollastri, Gianluca
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Date: Oct-2009
Abstract: The prediction of 1D structural properties of proteins is an important step toward the prediction of protein structure and function, not only in the ab initio case but also when homology information to known structures is available. Despite this the vast majority of 1D predictors do not incorporate homology information into the prediction process. We develop a novel structural alignment method, SAMD, which we use to build alignments of putative remote homologues that we compress into templates of structural frequency profiles. We use these templates as additional input to ensembles of recursive neural networks, which we specialise for the prediction of query sequences that show only remote homology to any Protein Data Bank structure. We predict four 1D structural properties – secondary structure, relative solvent accessibility, backbone structural motifs, and contact density. Secondary structure prediction accuracy, tested by five-fold cross-validation on a large set of proteins allowing less than 25% sequence identity between training and test set and query sequences and templates, exceeds 82%, outperforming its ab initio counterpart, other state-of-the-art secondary structure predictors (Jpred 3 and PSIPRED) and two other systems based on PSI-BLAST and COMPASS templates. We show that structural information from homologues improves prediction accuracy well beyond the Twilight Zone of sequence similarity, even below 5% sequence identity, for all four structural properties. Significant improvement over the extraction of structural information directly from PDB templates suggests that the combination of sequence and template information is more informative than templates alone.
Funding Details: Science Foundation Ireland
Health Research Board
Type of material: Journal Article
Publisher: Wiley InterScience
Journal: Proteins: Structure, Function, and Bioinformatics
Volume: 77
Issue: 1
Start page: 181
End page: 190
Copyright (published version): 2009 Wiley-Liss, Inc.
Keywords: AlignmentsHomology detectionSecondary structureSolvent accessibilityMachine learning
Subject LCSH: Sequence alignment (Bioinformatics)
Homology (Biology)
Machine learning
DOI: 10.1002/prot.22429
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Language: en
Status of Item: Peer reviewed
Appears in Collections:Computer Science Research Collection
CASL Research Collection

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