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.
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[Research Report] RR-8963, Inria Sophia Antipolis. 2016
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Soumis le : vendredi 14 octobre 2016 - 17:18:25
Dernière modification le : jeudi 11 janvier 2018 - 16:56:53

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Simon Marillet, Marie-Paule Lefranc, Pierre Boudinot, Frédéric Cazals. Novel structural parameters of Ig -Ag complexes yield a quantitative description of interaction specificity and binding affinity. [Research Report] RR-8963, Inria Sophia Antipolis. 2016. 〈hal-01381795〉

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