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

TY - JOUR

T1 - Promiscuous antibodies characterised by their physico-chemical properties

T2 - From sequence to structure and back

AU - Laffy, Julie M.J.

AU - Dodev, Tihomir

AU - Macpherson, Jamie A.

AU - Townsend, Catherine

AU - Lu, Hui Chun

AU - Dunn-Walters, Deborah

AU - Fraternali, Franca

PY - 2016/9/5

Y1 - 2016/9/5

N2 - 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.

AB - 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.

KW - Antibody CDRH3

KW - Binding promiscuity

KW - Conformational preferences

KW - ELISA

KW - Kidera factors

KW - Molecular modelling

KW - Monte Carlo simulations

U2 - 10.1016/j.pbiomolbio.2016.09.002

DO - 10.1016/j.pbiomolbio.2016.09.002

M3 - Article

SN - 0079-6107

JO - Progress in Biophysics and Molecular Biology

JF - Progress in Biophysics and Molecular Biology

ER -