Now showing 1 - 2 of 2
  • Publication
    Potential utility of docking to identify protein-peptide binding regions
    (University College Dublin. School of Computer Science and Informatics, 2013-05) ; ; ; ;
    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 regions involved in binding. We set out to determine if docking peptides to peptide binding domains would assist in these predictions. First, we investigated the docking of known short peptides to their native and non-native peptide binding domains. We then investigated the docking of overlapping peptides adjacent to the native peptide. We found only weak discrimination of docking scores between native peptide and adjacent peptides in this context with similar results for both ordered and disordered regions. Finally, we trained a bidirectional recurrent neural network using as input the peptide sequence, predicted secondary structure, Vina docking score and Pepsite score.We conclude that docking has only modest power to define the location of a peptide within a larger protein region known to contain it. However, this information can be used in training machine learning methods which may allow for the identification of peptide binding regions within a protein sequence.
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  • Publication
    Predicting Binding within Disordered Protein Regions to Structurally Characterised Peptide-Binding Domains
    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.
      207ScopusĀ© Citations 33