Evaluation of the coarse-grained OPEP force field for protein-protein docking.
BACKGROUND
Knowing the binding site of protein-protein complexes helps understand their function and shows possible regulation sites. The ultimate goal of protein-protein docking is the prediction of the three-dimensional structure of a protein-protein complex. Docking itself only produces plausible candidate structures, which must be ranked using scoring functions to identify the structures that are most likely to occur in nature.


METHODS
In this work, we rescore rigid body protein-protein predictions using the optimized potential for efficient structure prediction (OPEP), which is a coarse-grained force field. Using a force field based on continuous functions rather than a grid-based scoring function allows the introduction of protein flexibility during the docking procedure. First, we produce protein-protein predictions using ZDOCK, and after energy minimization via OPEP we rank them using an OPEP-based soft rescoring function. We also train the rescoring function for different complex classes and demonstrate its improved performance for an independent dataset.


RESULTS
The trained rescoring function produces a better ranking than ZDOCK for more than 50 % of targets, rising to over 70 % when considering only enzyme/inhibitor complexes.


CONCLUSIONS
This study demonstrates for the first time that energy functions derived from the coarse-grained OPEP force field can be employed to rescore predictions for protein-protein complexes.
Institute of Complex Systems: Structural Biochemistry (ICS-6), Forschungszentrum Jülich GmbH, Jülich, 52425 Germany.
Philipp
P
Kynast
Laboratoire de Biochimie Théorique, UPR 9080 CNRS, Institut de Biologie Physico-Chimique, Paris, 75005 France ; Institut Universitaire de France, 103 Boulevard Saint-Michel, Paris, 75005 France ; University Paris Diderot, Sorbonne Paris Cité, Paris, 75205 France.
Philippe
P
Derreumaux
Institute of Complex Systems: Structural Biochemistry (ICS-6), Forschungszentrum Jülich GmbH, Jülich, 52425 Germany ; Institute of Theoretical and Computational Chemistry, Heinrich Heine University Düsseldorf, Universitätsstr. 1, Düsseldorf, 40225 Germany.
Birgit
B
Strodel
Coarse graining; Flexible docking; Protein–protein docking; Rescoring