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Promiscuous antibodies characterised by their physico-chemical properties: From sequence to structure and back

Laffy, JMJ, Dodev, T, Macpherson, JA, Townsend, C, Lu, HC, Dunn-Walters, Deborah and Fraternali, F (2016) Promiscuous antibodies characterised by their physico-chemical properties: From sequence to structure and back Progress in Biophysics and Molecular Biology.

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Abstract

Human B cells produce antibodies, which bind to their cognate antigen based on distinct molecular properties of the antibody CDR loop. We have analysed a set of 10 antibodies showing a clear difference in their binding properties to a panel of antigens, resulting in two subsets of antibodies with a distinct binding phenotype. We call the observed binding multiplicity ‘promiscuous’ and selected physico-chemical CDRH3 characteristics and conformational preferences may characterise these promiscuous antibodies. To classify CDRH3 physico-chemical properties playing a role in their binding properties, we used statistical analyses of the sequences annotated by Kidera factors. To characterise structure-function requirements for antigen binding multiplicity we employed Molecular Modelling and Monte Carlo based coarse-grained simulations. The ability to predict the molecular causes of promiscuous, multi-binding behaviour would greatly improve the efficiency of the therapeutic antibody discovery process.

Item Type: Article
Subjects : Biosciences and Medicine
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Laffy, JMJUNSPECIFIEDUNSPECIFIED
Dodev, TUNSPECIFIEDUNSPECIFIED
Macpherson, JAUNSPECIFIEDUNSPECIFIED
Townsend, CUNSPECIFIEDUNSPECIFIED
Lu, HCUNSPECIFIEDUNSPECIFIED
Dunn-Walters, Deborahd.dunn-walters@surrey.ac.ukUNSPECIFIED
Fraternali, FUNSPECIFIEDUNSPECIFIED
Date : 14 September 2016
Identification Number : 10.1016/j.pbiomolbio.2016.09.002
Copyright Disclaimer : © 2017 Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/)
Uncontrolled Keywords : Antibody CDRH3, binding promiscuity, conformational preferences,, ELISA, Kidera Factors, Molecular Modelling, Monte Carlo simulations.
Depositing User : Symplectic Elements
Date Deposited : 16 Sep 2016 14:38
Last Modified : 13 Jul 2017 13:15
URI: http://epubs.surrey.ac.uk/id/eprint/812210

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