Moving pictures: Reassessing docking experiments with a dynamic view of protein interfaces

Proteins. 2021 Oct;89(10):1315-1323. doi: 10.1002/prot.26152. Epub 2021 May 31.


The modeling of protein assemblies at the atomic level remains a central issue in structural biology, as protein interactions play a key role in numerous cellular processes. This problem is traditionally addressed using docking tools, where the quality of the models is based on their similarity to a single reference experimental structure. However, using a static reference does not take into account the dynamic quality of the protein interface. Here, we used all-atom classical Molecular Dynamics simulations to investigate the stability of the reference interface for three complexes that previously served as targets in the CAPRI competition. For each one of these targets, we also ran MD simulations for ten models that are distributed over the High, Medium and Acceptable accuracy categories. To assess the quality of these models from a dynamic perspective, we set up new criteria which take into account the stability of the reference experimental protein interface. We show that, when the protein interfaces are allowed to evolve along time, the original ranking based on the static CAPRI criteria no longer holds as over 50% of the docking models undergo a category change (which can be either toward a better or a lower accuracy group) when reassessing their quality using dynamic information.

Keywords: docking; molecular dynamics simulations; protein interactions; protein interfaces.

MeSH terms

  • Binding Sites
  • Computational Biology / methods*
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Mapping
  • Proteins / chemistry*
  • Software


  • Proteins