Calculation of Therapeutic Antibody Viscosity with Computer Simulations
- Type: Conference Presentation
- Conference Type: AIChE Annual Meeting
- Presentation Date: November 10, 2021
- Duration: 18 minutes
- Skill Level: Intermediate
- PDHs: 0.50
High viscosity presents a challenge for manufacturing and drug delivery of therapeutic antibodies. The viscosity is determined by protein-protein interactions among many antibodies. Molecular simulation is a promising method to study protein-protein interactions; however, all-atom models do not allow the simulation of multiple molecules, which is necessary to compute viscosity directly. Coarse-grained models, on the other hand can do this. In this work, a 12-bead coarse-grained model was applied to study antibody interactions. Two adjustable parameters related to the short-range interactions on the variable and constant regions, were determined by fitting experimental data of 20 IgG1 monoclonal antibodies at 150 mg/mL. The root-mean-square deviation improved from 1 to 0.68, and the correlation coefficient improved from 0.63 to 0.87 compared to that of a previous model that assumed the short-range interactions were the same for all the beads. Our model is also able to calculate the viscosity over a wide range of concentrations without additional parameters. A tabulated viscosity based on our model is provided to facilitate antibody screening in early-stage design.
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|AIChE Member Credits||0.5|
|AIChE Graduate Student Members||Free|
|AIChE Undergraduate Student Members||Free|