title: Mutual information and variants for protein domain-domain contact prediction.
abstract: BACKGROUND
  Predicting protein contacts solely based on sequence information remains a challenging problem, despite the huge amount of sequence data at our disposal. Mutual Information (MI), an information theory measure, has been extensively employed and modified to identify residues within a protein (intra-protein) that are in contact. More recently MI and its variants have also been used in the prediction of contacts between proteins (inter-protein).
  
  
  METHODS
  Here we assess the predictive power of MI and variants for domain-domain contact prediction. We test original MI and these variants, which are called MIp, MIc and ZNMI, on 40 domain-domain test cases containing 10,753 sequences. We also propose and evaluate two new versions of MI that consider triangles of residues and the physiochemical properties of the amino acids, respectively.
  
  
  RESULTS
  We found that all versions of MI are skewed towards predicting surface residues. Since domain-domain contacts are on the surface of each domain, we considered only surface residues when attempting to predict contacts. Our analysis shows that MIc is the best current MI domain-domain contact predictor. At 20% recall MIc achieved a precision of 44.9% when only surface residues were considered. Our triangle and reduced alphabet variants of MI highlight the delicate trade-off between signal and noise in the use of MI for domain-domain contact prediction. We also examine a specific "successful" case study and demonstrate that here, when considering surface residues, even the most accurate domain-domain contact predictor, MIc, performs no better than random.
  
  
  CONCLUSIONS
  All tested variants of MI are skewed towards predicting surface residues. When considering surface residues only, we find MIc to be the best current MI domain-domain contact predictor. Its performance, however, is not as good as a non-MI based contact predictor, i-Patch. Additionally, the intra-protein contact prediction capabilities of MIc outperform its domain-domain contact prediction abilities.
authors.affiliation: Department of Statistics, University of Oxford, Oxford, UK.
authors.forename: Mireille
authors.initials: M
authors.lastname: Gomes
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hamer
authors.forename: Gesine
authors.initials: G
authors.lastname: Reinert
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Deane
mesh_terms: D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D011506:Proteins