Moving pictures: Reassessing docking experiments with a dynamic view of protein interfaces
Résumé
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 clas-
sical 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 dy-
namic 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.