Predicting Binding within Disordered Protein Regions to Structurally Characterised Peptide-Binding Domains

Title: Predicting Binding within Disordered Protein Regions to Structurally Characterised Peptide-Binding Domains
Authors: Khan, Waqasuddin
Duffy, Fergal J.
Pollastri, Gianluca
Shields, Denis C.
Mooney, Catherine
Permanent link: http://hdl.handle.net/10197/10071
Date: 3-Sep-2013
Online since: 2019-04-23T10:22:36Z
Abstract: Disordered regions of proteins often bind to structured domains, mediating interactions within and between proteins. However, it is difficult to identify a priori the short disordered regions involved in binding. We set out to determine if docking such peptide regions to peptide binding domains would assist in these predictions. We assembled a redundancy reduced dataset of SLiM (Short Linear Motif) containing proteins from the ELM database. We selected 84 sequences which had an associated PDB structures showing the SLiM bound to a protein receptor, where the SLiM was found within a 50 residue region of the protein sequence which was predicted to be disordered. First, we investigated the Vina docking scores of overlapping tripeptides from the 50 residue SLiM containing disordered regions of the protein sequence to the corresponding PDB domain. We found only weak discrimination of docking scores between peptides involved in binding and adjacent non-binding peptides in this context (AUC 0.58).Next, we trained a bidirectional recurrent neural network (BRNN) using as input the protein sequence, predicted secondary structure, Vina docking score and predicted disorder score. The results were very promising (AUC 0.72) showing that multiple sources of information can be combined to produce results which are clearly superior to any single source. We conclude that the Vina docking score alone has only modest power to define the location of a peptide within a larger protein region known to contain it. However, combining this information with other knowledge (using machine learning methods) clearly improves the identification of peptide binding regions within a protein sequence. This approach combining docking with machine learning is primarily a predictor of binding to peptide-binding sites, and is not intended as a predictor of specificity of binding to particular receptors.
Funding Details: European Commission
Science Foundation Ireland
University College Dublin
Type of material: Journal Article
Publisher: PLoS
Journal: PLoS ONE
Volume: 8
Issue: 9
Start page: e72838
Copyright (published version): 2013 the Authors
Keywords: ProteinsBinding sitesTripeptidesProtein sequencePeptide binding regions
DOI: 10.1371/journal.pone.0072838
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Computer Science Research Collection

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