Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Oct 15;28(20):2608-14.
doi: 10.1093/bioinformatics/bts493.

Application of asymmetric statistical potentials to antibody-protein docking

Ryan Brenke  1 , David R Hall, Gwo-Yu Chuang, Stephen R Comeau, Tanggis Bohnuud, Dmitri Beglov, Ora Schueler-Furman, Sandor Vajda, Dima Kozakov
Affiliations

Application of asymmetric statistical potentials to antibody-protein docking

Ryan Brenke et al. Bioinformatics. .

Abstract

Motivation: An effective docking algorithm for antibody-protein antigen complex prediction is an important first step toward design of biologics and vaccines. We have recently developed a new class of knowledge-based interaction potentials called Decoys as the Reference State (DARS) and incorporated DARS into the docking program PIPER based on the fast Fourier transform correlation approach. Although PIPER was the best performer in the latest rounds of the CAPRI protein docking experiment, it is much less accurate for docking antibody-protein antigen pairs than other types of complexes, in spite of incorporating sequence-based information on the location of the paratope. Analysis of antibody-protein antigen complexes has revealed an inherent asymmetry within these interfaces. Specifically, phenylalanine, tryptophan and tyrosine residues highly populate the paratope of the antibody but not the epitope of the antigen.

Results: Since this asymmetry cannot be adequately modeled using a symmetric pairwise potential, we have removed the usual assumption of symmetry. Interaction statistics were extracted from antibody-protein complexes under the assumption that a particular atom on the antibody is different from the same atom on the antigen protein. The use of the new potential significantly improves the performance of docking for antibody-protein antigen complexes, even without any sequence information on the location of the paratope. We note that the asymmetric potential captures the effects of the multi-body interactions inherent to the complex environment in the antibody-protein antigen interface.

Availability: The method is implemented in the ClusPro protein docking server, available at http://cluspro.bu.edu.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Patches of maximum hydrophobicity in an antibody–antigen complex. The structure is Jel42 Fab fragment complexed with HPr (PDB code 2jel). The antibody fragment is shown as the white solid model, with magenta patches representing the regions with maximum hydrophobicity. The HPr antigen is shown as a gray cartoon, with dark red patches as regions of maximum hydrophobicity. In the figure, the antibody CDR is oriented upward, showing that the CDR region includes strongly hydrophobic patches, but these do not interact with regions of maximum hydrophobicity on the HPr antigen
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Chen R., et al. ZDOCK: an initial-stage protein-docking algorithm. Proteins. 2003;52:80–87. - PubMed
    1. Chuang G., et al. DARS (Decoys as the Reference State) potentials for protein–protein docking. Biophys. J. 2008;95:4217–4227. - PMC - PubMed
    1. Clark L.A., et al. Trends in antibody sequence changes during the somatic hypermutation process. J. Immunol. 2006;177:333–340. - PubMed
    1. Comeau S.R., et al. ClusPro: an automated docking and discrimination method for the prediction of protein complexes. Bioinformatics. 2004;20:45–50. - PubMed
    1. Comeau S.R., et al. ClusPro: performance in CAPRI rounds 6-11 and the new server. Proteins. 2007;69:781–785. - PubMed

Publication types

-