Structure and Relaxation in Solutions of Monoclonal Antibodies

The Journal of Physical Chemistry. B
Gang WangJames Swan

Abstract

Reversible self-association of therapeutic antibodies is a key factor in high protein solution viscosities. In the present work, a coarse-grained computational model accounting for electrostatic, dispersion, and long-ranged hydrodynamic interactions of two model monoclonal antibodies is applied to understand the nature of self-association, predicting the solution microstructure and resulting transport properties of the solution. For the proteins investigated, the structure factor across a range of solution conditions shows quantitative agreement with neutron-scattering experiments. We observe a homogeneous, dynamical association of the antibodies with no evidence of phase separation. Calculations of self-diffusivity and viscosity from coarse-grained dynamic simulations show the appropriate trends with concentration but, respectively, over- and under-predict the experimentally measured values. By adding constraints to the self-associated clusters that rigidify them under flow, prediction of the transport properties is significantly improved with respect to experimental measurements. We hypothesize that these rigidity constraints are associated with missing degrees of freedom in the coarse-grained model resulting from patchy and ...Continue Reading

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Citations

Jan 23, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Rajat Dandekar, Arezoo M Ardekani
Oct 16, 2020·International Journal of Molecular Sciences·Manali S SawantPeter M Tessier
Apr 7, 2021·The Journal of Physical Chemistry. B·Hassan ShahfarChristopher J Roberts
May 18, 2020·Biophysical Journal·Saeed IzadiBenjamin T Walters
Mar 22, 2019·The Journal of Physical Chemistry Letters·Marco GrimaldoFrank Schreiber

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