Collaborative Research: Improving protein stability with non-traditional solvents

疫苗和抗体都是蛋白质。每个剂量的有效性取决于维持蛋白质的三维结构。在室温下，溶于水的蛋白质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策略是冷藏。这会减慢但不会停止变性。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变质。提高蛋白质的稳定性将为人类健康提供巨大的益处，特别是如果在室温下可以实现高稳定性。该项目将评估使用新的溶剂，称为离子液体，作为一种手段，以稳定蛋白质溶液。最终目标是长时间保持蛋白质活性。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。这种推广将加强学生进入和留在科学，工程和技术（STEM）计划的管道。蛋白质的状态由其局部分子内和分子间相互作用定义。这些包括溶剂环境的影响。向溶液中添加离子液体（IL）可以进一步稳定蛋白质。项目目标是确定溶剂的作用（即，IL-水组成）对蛋白质稳定性和结构的影响，以了解蛋白质溶解度行为，并确定IL-回收的蛋白质的活性。具体目标包括延长蛋白质在环境温度和升高温度下的稳定性的时间窗，以及在含IL溶液中延长储存后增加蛋白质活性的保留。该项目应该提供分子水平的见解对蛋白质结构和稳定性的具体影响。 模拟将放大实验结果的解释，并作为未来实验的指导。该奖项反映了NSF的法定使命，并被认为值得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来支持。

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.