posted on 2024-01-09, 21:08authored bySuman Saurabh, Qinkun Zhang, Zongyi Li, John M. Seddon, Cavan Kalonia, Jian R. Lu, Fernando Bresme
Monoclonal antibodies
(mAbs) are active components of therapeutic
formulations that interact with the water–vapor interface during
manufacturing, storage, and administration. Surface adsorption has
been demonstrated to mediate antibody aggregation, which leads to
a loss of therapeutic efficacy. Controlling mAb adsorption at interfaces
requires a deep understanding of the microscopic processes that lead
to adsorption and identification of the protein regions that drive
mAb surface activity. Here, we report all-atom molecular dynamics
(MD) simulations of the adsorption behavior of a full IgG1-type antibody
at the water/vapor interface. We demonstrate that small local changes
in the protein structure play a crucial role in promoting adsorption.
Also, interfacial adsorption triggers structural changes in the antibody,
potentially contributing to the further enhancement of surface activity.
Moreover, we identify key amino acid sequences that determine the
adsorption of antibodies at the water–air interface and outline
strategies to control the surface activity of these important therapeutic
proteins.