Mechanistic Insights into the Adsorption of Monoclonal Antibodies at the Water/Vapor Interface.
Mechanistic Insights into the Adsorption of Monoclonal Antibodies at the Water/Vapor Interface.
复制标题
单克隆抗体在水/蒸汽界面吸附的机理见解。
DOI：
10.1021/acs.molpharmaceut.3c00821
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发表时间：
2024
影响因子：
4.9
通讯作者：
Saurabh S
中科院分区：
文献类型：
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作者：
Saurabh S
单抗是治疗制剂的活性成分，在生产、储存和给药过程中与水蒸气界面相互作用。表面吸附已被证明介导抗体聚集，从而导致治疗效果的丧失。控制单抗在界面上的吸附需要深入了解导致吸附的微观过程，并识别驱动单抗表面活性的蛋白质区域。在这里，我们报告了全原子分子动力学(MD)模拟完整的IgG1型抗体在水/蒸汽界面的吸附行为。我们证明，蛋白质结构的微小局部变化在促进吸附方面起着至关重要的作用。此外，界面吸附触发抗体的结构变化，潜在地有助于进一步增强表面活性。此外，我们确定了决定抗体在水-空气界面上吸附的关键氨基酸序列，并概述了控制这些重要治疗性蛋白质表面活性的策略。
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.