Promiscuous antibodies characterised by their physico-chemical properties: From sequence to structure and back.
Prog Biophys Mol Biol
; 128: 47-56, 2017 09.
Article
in En
| MEDLINE
| ID: mdl-27639634
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chemical Phenomena
/
Antibodies
/
Antibody Specificity
Type of study:
Health_economic_evaluation
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Prog Biophys Mol Biol
Year:
2017
Document type:
Article
Affiliation country:
Reino Unido