Collaborative Research: Improving protein stability with non-traditional solvents

疫苗和抗体都是蛋白质。每次剂量的有效性取决于维持蛋白质的三维结构。在室温下，蛋白质溶解在水中，可以重新排列它们的结构，可能使它们变性。保存蛋白质结构最常用的方法是冷藏。这会减缓但不会停止变性。因此，任何疫苗的保质期都是有限的，导致每年数百万美元的疫苗和抗体遭到破坏。提高蛋白质的稳定性对人类健康有很大的好处，特别是如果能在室温下实现高稳定性。该项目将评估新型溶剂的使用，称为离子液体，作为稳定溶液中蛋白质的手段。最终目标是在较长时间内维持蛋白质活性。该项目将为本科生和高中生提供研究经验，重点是从代表性不足的人群中招募参与者。这种拓展将加强学生进入和留在科学、工程和技术（STEM）项目的管道。蛋白质的状态是由其局部分子内和分子间的相互作用决定的。这包括溶剂环境的影响。在溶液中加入离子液体（ILs）可以进一步稳定蛋白质。该项目的目标是通过光谱和原子模拟来确定溶剂（即il -水组成）对蛋白质稳定性和结构的作用，了解蛋白质的溶解度行为，并确定il回收蛋白质的活性。具体目标包括延长蛋白质在环境和高温下的稳定性时间窗口，并增加蛋白质在含il的溶液中延长储存后的活性保留。该项目将提供分子水平上对蛋白质结构和稳定性的具体影响的见解。模拟将扩大对实验结果的解释，并为未来的实验提供指导。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Vaccines and antibodies are proteins. The effectiveness of every dose depends on maintaining the three-dimensional structure of the protein. At room temperature, dissolved in water, proteins can rearrange their structure, possibly denaturing them. The strategy most often employed to preserve protein structure is refrigeration. This slows but does not stop denaturing. The shelf-life of any vaccine is therefore limited, leading to spoilage of millions of dollars of vaccines and antibodies each year. Improving protein stability would provide a great benefit to human health, especially if high stability could be achieved at room temperature. This project will evaluate the use of novel solvents, called ionic liquids, as a means to stabilize proteins in solution. The ultimate goal is to maintain protein activity for extended periods of time. This project will provide research experiences to undergraduates and high school students, with a focus on recruiting participants from underrepresented populations. This outreach will strengthen the pipeline of students entering and remaining in science, engineering and technology (STEM) programs. The state of a protein is defined by its local intra- and inter-molecular interactions. These include the effects of the solvent environment. The addition of ionic liquids (ILs) to the solution might further stabilize the protein. The project objectives are to determine the solvent role (i.e., IL-water composition) on protein stability and structure using spectroscopy and atomistic simulations, to understand protein solubility behavior, and to determine the activity of IL-recovered proteins. Specific goals include extending the time-window of protein stability at both ambient and elevated temperatures and increasing the retention of protein activity after extended storage in IL-containing solutions. This project should provide molecular-level insights into specific effects on protein structure and stability. Simulations will amplify the interpretation of experimental results and also serve as a guide to future experiments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.