Epitope mapping using combinatorial phage-display libraries: a graph-based algorithm.
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.
Mayrose
Itay
I
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel-Aviv 69978, Israel.
Shlomi
Tomer
T
Rubinstein
Nimrod D
ND
Gershoni
Jonathan M
JM
Ruppin
Eytan
E
Sharan
Roded
R
Pupko
Tal
T
D000465:Algorithms; D000906:Antibodies / Q000737:chemistry; D000941:Antigens / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D003196:Computer Graphics; D018604:Epitope Mapping / Q000379:methods*; D008958:Models, Molecular; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D025941:Protein Interaction Mapping / Q000379:methods
D000906:Antibodies; D000941:Antigens; D019151:Peptide Library; D010455:Peptides