Collaborative Research: The Thermodynamics of Protein Separations

Lenhoff05191这项研究的目标是使用单组分和多组分蛋白质溶液热力学的测量和机理模型作为开发合理的蛋白质分离和纯化策略的基础。这些策略将建立在对蛋白质-蛋白质相互作用以及如何在设计有效分离途径中操纵和利用它们的理解的基础上。这项研究将采用在早期赠款期间开发的许多方法，包括：测量蛋白质相互作用的方法，如自作用层析；计算蛋白质-蛋白质相互作用的方法，包括静电、弥散和水合作用；以及根据复杂的各向异性势计算相图的方法，如适用于蛋白质的方法。这项研究的一个特别重点领域将是将蛋白质相互作用的性质与所产生的相图以及在实践中观察到的无定形致密相的类型，如沉淀物和凝胶联系起来。该项目将支持博士后研究人员和研究生以及本科生的培训。在早期的资助期间，这些受训人员在学术和工业职业生涯中取得了成功，本科生也是许多出版物的共同作者。

Lenhoff0519191The objective of this research is to use measurements and mechanistic models of single and multicomponent protein solution thermodynamics as the basis for developing rational strategies for protein separation and purification. These strategies will build on the understanding of protein-protein interactions and of ways to manipulate and exploit them in designing effective separation pathways. This research will employ numerous approaches developed in earlier grant periods, including: methods to measure protein interactions, such as self-interaction chromatography; methods to calculate protein-protein interactions, including electrostatic, dispersion and hydration interactions; and methods to calculate phase diagrams from complex, anisotropic potentials such as those that apply to proteins. A particular area of emphasis in the research will be to relate the nature of protein interactions to the resulting phase diagram, as well as to the types of amorphous dense phases observed in practice, such as precipitates and gels.The project will support training of postdoctoral researchers and graduate students, as well as undergraduates. Such trainees in earlier grant periods have been successful in academic and industrial careers, and the undergraduates have been co-authors on numerous publications.