Format

Send to

Choose Destination
See comment in PubMed Commons below
BMC Bioinformatics. 2012 Sep 11;13:228. doi: 10.1186/1471-2105-13-228.

Protein-DNA docking with a coarse-grained force field.

Author information

1
Physics Department T38, Technical University Munich, James Franck Str. 1, 85748 Garching, Germany. piotr.setny@tum.de

Abstract

BACKGROUND:

Protein-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.

RESULTS:

We 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.

CONCLUSIONS:

We 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.

PMID:
22966980
PMCID:
PMC3522568
DOI:
10.1186/1471-2105-13-228
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Support Center