Novel structural parameters of Ig -Ag complexes yield a quantitative description of interaction specificity and binding affinity
Abstract
Antibody-antigen complexes challenge our understanding, as analyses to date
failed to unveil the key determinants of binding affinity and interaction specificity. We par-
tially fill this gap based on novel quantitative analyses using two standardized databases, the
IMGT/3Dstructure-DB and the structure affinity benchmark.
First, we introduce a statistical analysis of interfaces which enables the classification of ligand types
(protein, peptide, chemical; cross-validated classification error of 9.6%), and yield binding affinity
predictions of unprecedented accuracy (median absolute error of 0.878 kcal/mol). Second, we
exploit the contributions made by CDRs in terms of position at the interface and atomic packing
properties to show that in general, VH CDR3 and VL CDR3 make dominant contributions to
the binding affinity, a fact also shown to be consistent with the enthalpy - entropy compensation
associated with pre-configuration of CDR3.
Our work suggests that the affinity prediction problem could be solved from databases of high
resolution crystal structures of complexes with known affinity.
Origin : Files produced by the author(s)
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