Dissecting Interfaces of Antibody -Antigen Complexes: from Ligand Specific Features to Binding Affinity Predictions
Analyse des Interfaces de complexes Anticorps - Antigène: des caractéristiques propres au type de ligand à la prédiction d'affinité de liaison
Abstract
Adaptive immunity is based on antigen-specific lymphocyte responses, with in
particular B cells secreting seric immunoglobulins (IG) involved in the opsonization of bacteria
and the neutralization of viruses. At the heart of these mechanisms is the formation of IG -
Ag complexes, which challenge our understanding in terms of binding affinity and interaction
specificity.
In this work, we dissect the interfaces of IG - Ag complexes with high resolution crystal structures,
making a stride towards a better understanding of binding affinity and interaction specificity. First,
we present global interface statistics clearly distinguishing ligand types (proteins, peptides, chem-
ical compounds), and stressing the role of side chains. Second, we analyze the relative positions of
CDR with and without antigen, exhibiting a remarkably conserved pattern involving seven seams
between CDR. We also show that this generic pattern exhibits specific properties as a function of
the ligand type. Finally, we present binding affinity predictions of unprecedented accuracy, with a
median absolute error of 1.02 kcal/mol.
We anticipate that our findings will be of broad interest, not only in studying immune responses
at the structural level, but also in bio-engineering and IG design, with IG used extensively in
diagnostics and as well as therapeutic agents.
Origin : Files produced by the author(s)
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