Protein-DNA docking with a coarse-grained force field

Piotr Setny,Martin Zacharias,Ranjit Prasad Bahadur

doi:10.1186/1471-2105-13-228

Piotr Setny, Martin Zacharias + Show 1 more

Open Access

https://doi.org/10.1186/1471-2105-13-228

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Abstract

BackgroundProtein-DNA interactions are important for many cellular processes, however structural knowledge for a large fraction of known and putative complexes is still lacking. Computational docking methods aim at the prediction of complex architecture given detailed structures of its constituents. They are becoming an increasingly important tool in the field of macromolecular assemblies, complementing particularly demanding protein-nucleic acids X ray crystallography and providing means for the refinement and integration of low resolution data coming from rapidly advancing methods such as cryoelectron microscopy.ResultsWe present a new coarse-grained force field suitable for protein-DNA docking. The force field is an extension of previously developed parameter sets for protein-RNA and protein-protein interactions. The docking is based on potential energy minimization in translational and orientational degrees of freedom of the binding partners. It allows for fast and efficient systematic search for native-like complex geometry without any prior knowledge regarding binding site location.ConclusionsWe find that the force field gives very good results for bound docking. The quality of predictions in the case of unbound docking varies, depending on the level of structural deviation from bound geometries. We analyze the role of specific protein-DNA interactions on force field performance, both with respect to complex structure prediction, and the reproduction of experimental binding affinities. We find that such direct, specific interactions only partially contribute to protein-DNA recognition, indicating an important role of shape complementarity and sequence-dependent DNA internal energy, in line with the concept of indirect protein-DNA readout mechanism.

Highlights

Protein-DNA interactions are important for many cellular processes, structural knowledge for a large fraction of known and putative complexes is still lacking
Force field scoring performance was evaluated for each set by considering the percentage of hits found within n lowest energy solutions and calculating an area under the resulting curve (AUC) for n ∈ {1..100}
A coarse grained force field for protein-DNA docking was presented. It is compatible with previously developed parameter sets for protein-protein and proteinRNA docking, all suitable to use within the ATTRACT docking protocol

Summary

Introduction

Protein-DNA interactions are important for many cellular processes, structural knowledge for a large fraction of known and putative complexes is still lacking. Computational docking methods aim at the prediction of complex architecture given detailed structures of its constituents. They are becoming an increasingly important tool in the field of macromolecular assemblies, complementing demanding protein-nucleic acids X ray crystallography and providing means for the refinement and integration of low resolution data coming from rapidly advancing methods such as cryoelectron microscopy. For a large fraction of known and putative interactions structural knowledge is still lacking. Gene regulatory processes often involve weak and transient protein-DNA interactions for which experimental structure determination using X-ray crystallography can be difficult or impossible. It is desirable to be eventually able to answer the question if a protein may interact with DNA and how, without performing the experimental structure determination

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