Imperial College London
Alternate

Emeritus ProfessorJohnSeddon

Faculty of Natural Sciences, Department of Chemistry

Senior Research Investigator
 
 
 
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Contact

 

+44 (0)20 7594 5797j.seddon Website

 
 
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Location

 

207EMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Saurabh:2022:10.1021/acs.molpharmaceut.2c00453,
author = {Saurabh, S and Kalonia, C and Li, Z and Hollowell, P and Waigh, T and Li, P and Webster, J and Seddon, JM and Lu, JR and Bresme, F},
doi = {10.1021/acs.molpharmaceut.2c00453},
journal = {Molecular Pharmaceutics},
title = {Understanding the stabilizing effect of histidine on mAb aggregation: a molecular dynamics study.},
url = {http://dx.doi.org/10.1021/acs.molpharmaceut.2c00453},
volume = {19},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Histidine, a widely used buffer in monoclonal antibody (mAb) formulations, is known to reduce antibody aggregation. While experimental studies suggest a nonelectrostatic, nonstructural (relating to secondary structure preservation) origin of the phenomenon, the underlying microscopic mechanism behind the histidine action is still unknown. Understanding this mechanism will help evaluate and predict the stabilizing effect of this buffer under different experimental conditions and for different mAbs. We have used all-atom molecular dynamics simulations and contact-based free energy calculations to investigate molecular-level interactions between the histidine buffer and mAbs, which lead to the observed stability of therapeutic formulations in the presence of histidine. We reformulate the Spatial Aggregation Propensity index by including the buffer-protein interactions. The buffer adsorption on the protein surface leads to lower exposure of the hydrophobic regions to water. Our analysis indicates that the mechanism behind the stabilizing action of histidine is connected to the shielding of the solvent-exposed hydrophobic regions on the protein surface by the buffer molecules.
AU  - Saurabh,S
AU  - Kalonia,C
AU  - Li,Z
AU  - Hollowell,P
AU  - Waigh,T
AU  - Li,P
AU  - Webster,J
AU  - Seddon,JM
AU  - Lu,JR
AU  - Bresme,F
DO  - 10.1021/acs.molpharmaceut.2c00453
PY  - 2022///
SN  - 1543-8384
TI  - Understanding the stabilizing effect of histidine on mAb aggregation: a molecular dynamics study.
T2  - Molecular Pharmaceutics
UR  - http://dx.doi.org/10.1021/acs.molpharmaceut.2c00453
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35946408
UR  - https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.2c00453
UR  - http://hdl.handle.net/10044/1/98990
VL  - 19
ER  -
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