Application of asymmetric statistical potentials to antibody-protein docking.
BACKGROUND
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.


BACKGROUND
The method is implemented in the ClusPro protein docking server, available at http://cluspro.bu.edu.
Department of Biomedical Engineering, Boston University, Boston, MA, USA.
Ryan
R
Brenke
David R
DR
Hall
Gwo-Yu
GY
Chuang
Stephen R
SR
Comeau
Tanggis
T
Bohnuud
Dmitri
D
Beglov
Ora
O
Schueler-Furman
Sandor
S
Vajda
Dima
D
Kozakov
D000465:Algorithms; D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000378:metabolism; D003627:Data Interpretation, Statistical; D005583:Fourier Analysis; D051188:Knowledge Bases; D062105:Molecular Docking Simulation / Q000379:methods*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D000936:Antigen-Antibody Complex; D011506:Proteins