建模色谱通过分子动力学模拟与树脂碎片结合结合
Vitali Stanevich1, Oluyemi Oyeniran2, Sandeep Somani3
1Protein Therapeutics API Development, Janssen Research & Development, LLC, a Johnson & Johnson company, Malvern, Pennsylvania 19355, United States.
The journal of physical chemistry. B
|May 29, 2024
概括
这项研究引入了一种分子动力学模拟方法,用于预测蛋白质与色谱树脂的相互作用,有助于生物制药净化. 该方法准确地预测了蛋白质的保留和化顺序,减少了实验力度.
科学领域:
- 生物物理化学 生物物理化学
- 计算化学是一种计算化学.
- 化学工程是化学工程的组成部分.
背景情况:
- 精确的蛋白质树脂相互作用建模对于优化生物制药净化过程至关重要.
- 目前的方法往往需要大量的实验数据,增加时间和成本.
研究的目的:
- 开发和验证基于分子动力学模拟的方法,用于预测染色体树脂上的蛋白质相互作用点和保留时间.
- 建立基于物理的模型,用于指导生物技术和制药行业的净化条件的选择.
主要方法:
- 模仿色谱树脂与不受约束的配体和模拟蛋白质-配体相互作用在明确的溶剂使用复制品交换分子动力学与质量再分配 (REMD-HMR).
- 从模拟轨迹计算连接体相互作用表面,并将它们与实验保留时间相关联.
- 将该协议应用于乌比奎突变体,随后应用于具有已知的Capto MMC化时间的六种蛋白质,分析残留级物理化学描述剂.
主要成果:
- 模拟协议成功预测了Capto MMC树脂上的蛋白质的相互作用点和保留时间.
- 基于芳性和疏水性的一种线性模型准确地预测了基于模拟衍生的描述符的蛋白质化顺序.
- 该方法显示出对异常值的稳定性和与实验数据的高相关性.
结论:
- 开发的基于物理学的建模方法为预测蛋白质树脂相互作用和优化基于色谱的净化提供了可靠和高效的方法.
- 这种方法减少了对大型实验数据集的需求,并且可以适应各种树脂和生物分子.
更多相关视频
相关概念视频
01:03Affinity Chromatography
620
Affinity chromatography is a powerful technique extensively utilized for separating and purifying specific biomolecules from complex mixtures. It capitalizes on the highly selective binding between an analyte and its counterpart, such as antibody-antigen interactions. The counterpart is immobilized on the stationary phase, forming an affinity column. The stationary phase typically consists of solid support, such as agarose or porous glass beads, immobilizing the affinity ligand. The mobile...
620
02:00Molecular Models
38.2K
Physical models representing molecular architectures of chemical compounds play essential roles in understanding chemistry. The use of molecular models makes it easier to visualize the structures and shapes of atoms and molecules.
38.2K
01:10Chromatography: Introduction
4.3K
Chromatography is a technique used to separate compounds based on differences of partitioning between two phases, the stationary phase and the mobile phase.
The phase in which the compounds linger or on which the compounds adsorb is called the stationary phase, whereas the mobile phase is the solvent that carries the solutes to be analyzed. In traditional column chromatography, the mixture flows through the stationary phase, and the compounds partition between the stationary and mobile phases...
The phase in which the compounds linger or on which the compounds adsorb is called the stationary phase, whereas the mobile phase is the solvent that carries the solutes to be analyzed. In traditional column chromatography, the mixture flows through the stationary phase, and the compounds partition between the stationary and mobile phases...
4.3K