Phase-Sensitive Chiral Sum Frequency Generation Vibrational Spectroscopy for Probing Protein Hydration at Aqueous Interfaces

用于探测水界面蛋白质水合的相敏手性和频发生振动光谱

• 批准号: 2108690
• 负责人: Elsa Chui-Ying Yan
• 金额: $ 43.5万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2108690&HistoricalAwards=false
• 关键词: Phase; Sensitive; Chiral; Sum; Frequency

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Professor Elsa Chui-Ying Yan of Yale University is studying protein interactions with water on surfaces by developing a new optical method. Proteins are molecular machineries that carry out biological functions. Many of them are situated on cell surfaces for critical life processes, such as cell communication, cell adhesion, and immunological response. These proteins are excellent targets for drug design and the recent success in developing the COVID-19 vaccine is an example. In industries, protein stability upon interactions with surfaces can greatly impact product quality, such as food packaging and drug delivery systems. Also, proteins are incorporated on surfaces for making biosensors and molecular devices. Therefore, being able to predict protein behaviors on various surfaces can help advance fundamental knowledge and develope new drugs and materials. Nonetheless, proteins on surfaces cannot function by themselves. Not only do they interact with the surface materials (e.g., cell membrane and plastic packages), they are also integrated with surrounding water molecules. These water molecules determine protein structures and functions, and thus must be considered to fully understand and predict protein behaviors. Professor Yan will develop a new optical technique with unprecedented selectivity for detecting water molecules and their interactions with proteins on surfaces. Combining experimental and computational methods, Professor Yan will develop approaches to generate detailed descriptions of these water molecules interacting with various types of proteins on surfaces. Professor Yan will provide training opportunities to students at various levels in conducting scientific research and organize students to reach out to a neighborhood high school to support their STEM education program and hold panel discussions on STEM career opportunities. The project will develop external heterodyne chiral vibrational sum frequency (SFG) generation spectroscopy to probe protein hydration at interfaces. This method is expected to have the advantages of being in situ, real-time, and label-free. More importantly, it will provide unique selectivity to water molecules surrounding proteins that are in folded chiral structures without interference of background signals from interfacial and bulk water. The project will construct an external heterodyne SFG spectrometer to acquire water O-H stretching spectra at the air/water interface in the presence of proteins that with attention to their secondary, tertiary, and quaternary structures. Molecular dynamics (MD) models being constructed at the interface will be used to simulate the phase-resolved chiral SFG spectra. The comparison of the experimental and computational spectra in conjunction with analyses of the MD trajectories will allow for extraction of information about topology and local interactions of water molecules around the proteins. Finally, the combined experimental and computational approaches will be used to investigate changes in water structures during protein denaturation on surfaces.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.

耶鲁大学的艾尔莎崔英教授在化学系生命过程化学研究计划的支持下，正在开发一种新的光学方法，研究蛋白质与表面水的相互作用。蛋白质是执行生物功能的分子机器。它们中的许多位于细胞表面，用于关键的生命过程，如细胞通讯，细胞粘附和免疫反应。这些蛋白质是药物设计的绝佳靶标，最近成功开发COVID-19疫苗就是一个例子。在工业中，蛋白质与表面相互作用后的稳定性可以极大地影响产品质量，例如食品包装和药物输送系统。此外，蛋白质被结合在表面上用于制造生物传感器和分子装置。因此，能够预测蛋白质在各种表面上的行为可以帮助推进基础知识和开发新的药物和材料。尽管如此，表面上的蛋白质本身不能发挥作用。它们不仅与表面材料相互作用（例如，细胞膜和塑料包装），它们也与周围的水分子结合在一起。这些水分子决定蛋白质的结构和功能，因此必须考虑到充分理解和预测蛋白质的行为。严教授将开发一种新的光学技术，具有前所未有的选择性，用于检测水分子及其与表面蛋白质的相互作用。结合实验和计算方法，严教授将开发方法来生成这些水分子与表面上各种类型蛋白质相互作用的详细描述。严教授将为不同层次的学生提供科学研究的培训机会，并组织学生到附近的高中支持他们的STEM教育计划，并就STEM职业机会举行小组讨论。该项目将开发外部外差手性振动和频（SFG）产生光谱，以探测界面处的蛋白质水合作用。该方法有望具有原位、实时、无标记等优点。更重要的是，它将提供独特的选择性周围的水分子的蛋白质是在折叠的手性结构，没有干扰的背景信号，从界面和本体水。该项目将构建一个外部外差SFG光谱仪，以在存在蛋白质的情况下获得空气/水界面处的水O-H伸缩光谱，并关注其二级，三级和四级结构。分子动力学（MD）模型正在建设的界面将被用来模拟相位分辨的手征SFG光谱。结合MD轨迹分析的实验和计算光谱的比较将允许提取关于蛋白质周围的水分子的拓扑结构和局部相互作用的信息。最后，结合实验和计算的方法将被用来调查蛋白质变性过程中的水结构在surface.This奖项反映了NSF的法定使命的变化，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

项目成果

Characterizing Interfaces by Voronoi Tessellation

通过 Voronoi 曲面细分表征界面

• DOI: 10.1021/acs.jpclett.3c01159
• 发表时间: 2023
• 期刊: The Journal of Physical Chemistry Letters
• 作者: Konstantinovsky, Daniel;Yan, Elsa C.;Hammes-Schiffer, Sharon
• 通讯作者: Hammes-Schiffer, Sharon

Design of an Electrostatic Frequency Map for the NH Stretch of the Protein Backbone and Application to Chiral Sum Frequency Generation Spectroscopy

蛋白质主链 NH 拉伸静电频率图的设计及其在手性和频发生光谱中的应用

• DOI: 10.1021/acs.jpcb.3c00217
• 发表时间: 2023
• 期刊: The Journal of Physical Chemistry B
• 作者: Konstantinovsky, Daniel;Perets, Ethan A.;Santiago, Ty;Olesen, Kristian;Wang, Zhijie;Soudackov, Alexander V.;Yan, Elsa C.Y.;Hammes-Schiffer, Sharon
• 通讯作者: Hammes-Schiffer, Sharon