期刊
MOLECULAR PHARMACEUTICS
卷 19, 期 2, 页码 508-519出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.1c00627
关键词
monoclonal antibodies; light scattering; small-angle X-ray scattering; Monte Carlo simulations; course-grained modeling; osmotic second virial coefficient; structure factor; colloidal stability; protein aggregation
资金
- European Union's Horizon 2020 Marie Sklodowska-Curie Actions [675074]
- Swedish Research Foundation
The self-interactions of two monoclonal antibodies were studied using light scattering, small-angle X-ray scattering, and Monte Carlo simulations. By comparing simulation and experimental results, insights into the mAbs' self-interaction properties were obtained, with a focus on the role of ion binding and charged patches on the mAb surfaces. These models provide useful information about mAbs' self-interaction properties and assist in screening conditions for colloidal stability.
Using light scattering (LS), small-angle X- ray scattering (SAXS), and coarse-grained Monte Carlo (MC) simulations, we studied the self-interactions of two monoclonal antibodies (mAbs), PPI03 and PPI13. With LS measurements, we obtained the osmotic second virial coefficient, B-22, and the molecular weight, Mw, of the two mAbs, while with SAXS measurements, we studied the mAbs' self-interaction behavior in the high protein concentration regime up to 125 g/L. Through SAXS-derived coarse-grained representations of the mAbs, we performed MC simulations with either a one-protein or a twoprotein model to predict B-22. By comparing simulation and experimental results, we validated our models and obtained insights into the mAbs' self-interaction properties, highlighting the role of both ion binding and charged patches on the mAb surfaces. Our models provide useful information about mAbs' self-interaction properties and can assist the screening of conditions driving to colloidal stability.
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