Structure-based evaluation of in silico predictions of protein-protein interactions using Comparative Docking

Bioinformatics. 2007 Mar 1;23(5):573-81. doi: 10.1093/bioinformatics/btl661. Epub 2007 Jan 18.


Motivation: Due to the limitations in experimental methods for determining binary interactions and structure determination of protein complexes, the need exists for computational models to fill the increasing gap between genome sequence information and protein annotation. Here we describe a novel method that uses structural models to reduce a large number of in silico predictions to a high confidence subset that is amenable to experimental validation.

Results: A two-stage evaluation procedure was developed, first, a sequence-based method assessed the conservation of protein interface patches used in the original in silico prediction method, both in terms of position within the primary sequence, and in terms of sequence conservation. When applying the most stringent conditions it was found that 20.5% of the data set being assessed passed this test. Secondly, a high-throughput structure-based docking evaluation procedure assessed the soundness of three dimensional models produced for the putative interactions. Of the data set being assessed, 8264 interactions or over 70% could be modelled in this way, and 27% of these can be considered 'valid' by the applied criteria. In all, 6.9% of the interactions passed both the tests and can be considered to be a high confidence set of predicted interactions, several of which are described.


Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Azotobacter vinelandii / enzymology
  • Computer Simulation
  • Databases, Protein
  • Dihydrolipoamide Dehydrogenase / chemistry
  • Insulin Receptor Substrate Proteins
  • Models, Molecular*
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism
  • Protein Conformation*
  • Protein Interaction Mapping / methods*
  • Proteins / chemistry
  • Receptor, Insulin / chemistry
  • Receptor, Insulin / metabolism
  • Structure-Activity Relationship


  • Insulin Receptor Substrate Proteins
  • Phosphoproteins
  • Proteins
  • Dihydrolipoamide Dehydrogenase
  • Receptor, Insulin