Epitope mapping using combinatorial phage-display libraries: a graph-based algorithm

Abstract

A phage-display library of random peptides is a combinatorial experimental technique that can be harnessed for studying antibody–antigen interactions. In this technique, a phage peptide library is scanned against an antibody molecule to obtain a set of peptides that are bound by the antibody with high affinity. This set of peptides is regarded as mimicking the genuine epitope of the antibody's interacting antigen and can be used to define it. Here we present PepSurf, an algorithm for mapping a set of affinity-selected peptides onto the solved structure of the antigen. The problem of epitope mapping is converted into the task of aligning a set of query peptides to a graph representing the surface of the antigen. The best match of each peptide is found by aligning it against virtually all possible paths in the graph. Following a clustering step, which combines the most significant matches, a predicted epitope is inferred. We show that PepSurf accurately predicts the epitope in four cases for which the epitope is known from a solved antibody–antigen co-crystal complex. We further examine the capabilities of PepSurf for predicting other types of protein–protein interfaces. The performance of PepSurf is compared to other available epitope mapping programs.

An Oxycodone Conjugate Vaccine Elicits Drug-Specific Antibodies that Reduce Oxycodone Distribution to Brain and Hot-Plate Analgesia

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Caracterización in silico de la proteínaLeishmanolisina (GP63) de Leishmaniabraziliensis y búsqueda de epitopes de utilidadpara el desarrollo de vacunas

“…Para determinar los principales parámetros bioquímicos de la enzima en estudio, se empleó la herramienta ProtParam del ExPASy (http://web.expasy.org/protparam/) (7). (14), determinándose su ubicación en la proteína en estudio.…”

Characterization of mAb6-9-1 monoclonal antibody against hemagglutinin of avian influenza virus H5N1 and its engineered derivative, single-chain variable fragment antibody

“…The Pepitope server (http://pepitope.tau.ac.il/) (Mayrose et al, 2007a) was used to map the selected peptides onto the 3D model of HA from A/swan/Poland/305-135V08/2006 (H5N1). Using the consensus methodology, both PepSurf (Mayrose et al, 2007b) and Mapitope algorithms (Bublil et al, 2007) were executed and their results combined into a single prediction including only residues predicted to be a part of the epitope in both algorithms. Mapping results were compared with the surface of the H5 HA structural model using UCSF Chimera (v1.11).…”