Oct 12, 2012

Application of asymmetric statistical potentials to antibody-protein docking

Bioinformatics
Ryan BrenkeDima Kozakov

Abstract

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. 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 u...Continue Reading

Mentioned in this Paper

Tryptophan
Biological Products
Binding Sites, Antibody
Vaccines
Complex (molecular entity)
Plasma Protein Binding Capacity
Docking -molecular Interaction
Fourier Transform
Data Interpretation, Statistical
Antigens

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