Development and experimental validation of a molecular dynamic simulation method to predict adsorption isotherms of proteins

预测蛋白质吸附等温线的分子动力学模拟方法的开发和实验验证

• 批准号: 461481804
• 负责人: Dr.-Ing. Sven Jakobtorweihen
• 金额: --
• 依托单位: Institut für Chemische Reaktionstechnik V-2
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/461481804?language=en
• 关键词: Development; experimental; validation; molecular; dynamic

The production of proteins as biopharmaceuticals is a significant and growing branch of the pharmaceutical industry. According to the state of the art for such processes, product purification is carried out via various chromatographic methods. Their development is based on extensive and complex experimental work. In this project, experimental methods and molecular dynamic (MD) simulations will be closely intertwined to describe the ion-exchange adsorption of proteins. A comprehensive experimental characterization of existing adsorbents as well as the description of existing adsorption properties will be performed. In parallel, MD simulations of adsorption are performed and the descriptive parameters of protein adsorption are determined using the SMA model as an example. This provides the basis for subsequent description of an optimized adsorbent structure.Within this research project, MD methods are successfully applied to describe the ion-exchange adsorption of proteins. Therefore, a validated model for the complete description of an adsorption isotherm at different process parameters will be developed. This will allow for the complete prediction of the adsorption isotherms of proteins in silico for the first time. Furthermore, individual interaction centers on the model proteins are characterized, in order to describe new adsorbents with improved adsorption properties.

作为生物制药的蛋白质生产是制药工业的一个重要且不断增长的分支。根据这些方法的现有技术，产物纯化通过各种色谱方法进行。它们的开发是基于广泛而复杂的实验工作。在这个项目中，实验方法和分子动力学（MD）模拟将紧密交织在一起，以描述蛋白质的离子交换吸附。将进行现有吸附剂的综合实验表征以及现有吸附性能的描述。平行地，进行吸附的MD模拟，并且使用SMA模型作为示例来确定蛋白质吸附的描述性参数。本研究将分子动力学方法成功地应用于蛋白质的离子交换吸附。因此，将开发一个经过验证的模型，用于完整描述不同工艺参数下的吸附等温线。这将允许第一次在计算机上完整预测蛋白质的吸附等温线。此外，个别的相互作用中心的模型蛋白质的特征在于，为了描述新的吸附剂具有改善的吸附性能。