粘度
航程(航空)
工作(物理)
热力学
材料科学
常量(计算机编程)
化学
计算机科学
物理
复合材料
程序设计语言
作者
Pin‐Kuang Lai,James W. Swan,Bernhardt L. Trout
出处
期刊:mAbs
[Informa]
日期:2021-01-01
卷期号:13 (1)
被引量:25
标识
DOI:10.1080/19420862.2021.1907882
摘要
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 based on Swan and coworkers (J. Phys. Chem. B 2018, 122, 2867-2880) 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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