Collaborative Research: Molecular basis for protein sorption in polymer-modified chromatographic media

合作研究：聚合物改性色谱介质中蛋白质吸附的分子基础

• 批准号: 1264696
• 负责人: Igal Szleifer
• 金额: $ 22.5万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1264696&HistoricalAwards=false
• 关键词: Collaborative; Research; Molecular; basis; protein

Lenhoff / Szleifer1263966 / 1264696The goal of the collaborative project is to quantify the functional characteristics of polymer-derivatized media (PDM) to gain an understanding of the mechanism of protein sorption and transport within the matrix using experimental and computational methods. The focus is on ion exchange polymers that allow for both partitioning and surface sorption. The research is organized around three specific aims:1) Determine comparative sorption and transport characteristics for proteins on PDM with different architectures.2) Measure microscopic characteristics of the sorption process and the sorbed state as a guide to identification and analysis of sorption and transport mechanisms.3) Generalize and apply molecular theories to describe the sorption equilibrium and kinetics of proteins in PDM.The first two aims cover generation of a wide array of experimental data that will make possible a detailed mechanistic analysis of the phenomena involved. These two aims differ in that the first covers chromatographic behavior that is directly meaningful in assessing function under normal process conditions, while the second involves more fine-grained, primarily microscopic methods that are intended to resolve ambiguities regarding possible mechanisms. The third aim will employ realistic, state-of-the art molecular modeling to simulate equilibrium and kinetic behavior of proteins in polymer-derivatized ion-exchange media and provide a rigorous basis for resolving mechanistic uncertainties. Once completed, these studies will allow the development of simpler relationships suitable for routine use in chromatographic modeling, and these methods will then be applied to predicting the efficacy of separation of a model mixture. Successful completion of the investigation will yield structure-function relations that can facilitate explanation of observed performance trends, optimization of materials selection for specific separations, and design of novel adsorbents. Broader impacts. The results of the project are expected to elucidate the mechanisms of actions of PDM and hence benefit research and development in the biotechnology and pharmaceutical industries. The work may help resolve important issues such as slow elution that currently bedevil some applications. For stationary-phase manufacturers, a clearer understanding of the underlying mechanisms of action can guide development of new adsorbents; the PIs have collaborations with relevant companies. While the findings of the research will be disseminated mainly by publication in peer-reviewed journals, the PIs will also make the larger output from the research available to the research community, including software to apply the molecular theory to chromatographic processes. The impact in student training in research will be enriched by the multidisciplinary and multisite collaboration.

Lenhoff / szleifer1263966 / 1264696协作项目的目标是量化聚合物衍生介质（PDM）的功能特征，以便使用实验和计算方法了解矩阵内蛋白质吸附和运输机制。重点是允许分配和表面吸附的离子交换聚合物。 The research is organized around three specific aims:1) Determine comparative sorption and transport characteristics for proteins on PDM with different architectures.2) Measure microscopic characteristics of the sorption process and the sorbed state as a guide to identification and analysis of sorption and transport mechanisms.3) Generalize and apply molecular theories to describe the sorption equilibrium and kinetics of proteins in PDM.The first two aims cover generation of a wide array of实验数据将使涉及现象的详细机械分析成为可能。这两个目标的不同之处在于，第一个涵盖的色谱行为在正常过程条件下评估功能直接有意义，而第二个则涉及更细粒度的，主要是微观方法，这些方法旨在解决有关可能机制的歧义。第三个目标将采用逼真的，最先进的分子建模来模拟聚合物衍生化离子交换介质中蛋白质的平衡和动力学行为，并为解决机械不确定性提供了严格的基础。完成后，这些研究将允许建立更简单的关系，适合在色谱建模中常规使用，然后将这些方法应用于预测模型混合物分离的功效。成功完成调查将产生结构功能关系，以促进观察到的性能趋势，优化特定分离的材料选择以及新型吸附剂的设计。 更广泛的影响。 该项目的结果有望阐明PDM的作用机制，从而使生物技术和制药行业的研发受益。 这项工作可能有助于解决重要的问题，例如当前Bedevil某些应用的缓慢洗脱。对于固定相制造商，对行动的潜在机制有更清晰的了解可以指导新的吸附剂的发展； PI与相关公司合作。 虽然研究结果将主要通过同行评审期刊的出版物进行传播，但PIS还将使研究社区可用的研究更大，包括将分子理论应用于色谱过程的软件。 多学科和多站点的合作将使学生培训的研究影响丰富。