Improved side-chain modeling for protein-protein docking

Protein Sci. 2005 May;14(5):1328-39. doi: 10.1110/ps.041222905. Epub 2005 Mar 31.


Success in high-resolution protein-protein docking requires accurate modeling of side-chain conformations at the interface. Most current methods either leave side chains fixed in the conformations observed in the unbound protein structures or allow the side chains to sample a set of discrete rotamer conformations. Here we describe a rapid and efficient method for sampling off-rotamer side-chain conformations by torsion space minimization during protein-protein docking starting from discrete rotamer libraries supplemented with side-chain conformations taken from the unbound structures, and show that the new method improves side-chain modeling and increases the energetic discrimination between good and bad models. Analysis of the distribution of side-chain interaction energies within and between the two protein partners shows that the new method leads to more native-like distributions of interaction energies and that the neglect of side-chain entropy produces a small but measurable increase in the number of residues whose interaction energy cannot compensate for the entropic cost of side-chain freezing at the interface. The power of the method is highlighted by a number of predictions of unprecedented accuracy in the recent CAPRI (Critical Assessment of PRedicted Interactions) blind test of protein-protein docking methods.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Models, Molecular
  • Protein Conformation
  • Proteins / chemistry*


  • Proteins