Promiscuous antibodies characterised by their physico-chemical properties: From sequence to structure and back. (September 2017)

• Record Type: Journal Article
• Authors: Laffy, Julie M.J.; Dodev, Tihomir; Macpherson, Jamie A.; Townsend, Catherine; Lu, Hui Chun; Dunn-Walters, Deborah; Fraternali, Franca
• Is Part Of: Progress in biophysics and molecular biology. Volume 128(2017)
• Page Start: 47
• Page End: 56
• Publication Date: 2017-09
• Subjects: Antibody CDRH3 -- Binding promiscuity -- Conformational preferences -- ELISA -- Kidera factors -- Molecular modelling -- Monte Carlo simulations; Biophysics -- Periodicals; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular Biology -- Periodicals; Biophysique -- Périodiques; Biochimie -- Périodiques; 571.4
• DOI: 10.1016/j.pbiomolbio.2016.09.002
• Languages: English
• ISSNs: 0079-6107

Abstract

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.