Collaborative Research: The Thermodynamics of Protein Separations

本研究的目的是利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制定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-蛋白质相互作用的理解以及在设计有效分离途径时操纵和利用它们的方法的基础上。这项研究将采用在早期拨款期间开发的许多方法，包括：测量蛋白质相互作用的方法，如自相互作用色谱法；蛋白质-蛋白质相互作用的计算方法，包括静电、分散和水合作用；以及从复杂的各向异性电位（如适用于蛋白质的电位）计算相图的方法。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得到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，这些受训者在学术和工业生涯中都取得了成功，本科生在许多出版物中都是合著者。

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.