Towards the prediction of protein interaction partners using physical docking

Mol Syst Biol. 2011 Feb 15;7:469. doi: 10.1038/msb.2011.3.

Abstract

Deciphering the whole network of protein interactions for a given proteome ('interactome') is the goal of many experimental and computational efforts in Systems Biology. Separately the prediction of the structure of protein complexes by docking methods is a well-established scientific area. To date, docking programs have not been used to predict interaction partners. We provide a proof of principle for such an approach. Using a set of protein complexes representing known interactors in their unbound form, we show that a standard docking program can distinguish the true interactors from a background of 922 non-redundant potential interactors. We additionally show that true interactions can be distinguished from non-likely interacting proteins within the same structural family. Our approach may be put in the context of the proposed 'funnel-energy model'; the docking algorithm may not find the native complex, but it distinguishes binding partners because of the higher probability of favourable models compared with a collection of non-binders. The potential exists to develop this proof of principle into new approaches for predicting interaction partners and reconstructing biological networks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Binding Sites
  • Computational Biology / methods*
  • Computer Simulation
  • Databases, Protein*
  • Models, Molecular
  • Protein Binding
  • Protein Conformation*
  • Protein Interaction Mapping*
  • Proteins / chemistry*
  • Proteins / metabolism

Substances

  • Proteins