Journal
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
Volume 128, Issue -, Pages 47-56Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbiomolbio.2016.09.002
Keywords
Antibody CDRH3; Binding promiscuity; Conformational preferences; ELISA; Kidera factors; Molecular modelling; Monte Carlo simulations
Categories
Funding
- MRC/BBSRC programme [MR/L01257X/1]
- Dunhill Medical Trust [R279/0213]
- BBSRC CASE award [BB/L015845/1]
- Biotechnology and Biological Sciences Research Council [1525051] Funding Source: researchfish
- Medical Research Council [MR/L01257X/1, MR/L01257X/2] Funding Source: researchfish
- The Dunhill Medical Trust [R279/0213] Funding Source: researchfish
- MRC [MR/L01257X/2, MR/L01257X/1] Funding Source: UKRI
Ask authors/readers for more resources
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 physicochemical 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. (C) 2017 Elsevier Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available