D3SC: Nonlinear Optical Analysis of Proteins in Glasses

D3SC：玻璃中蛋白质的非线性光学分析

• 批准号: 2004046
• 负责人: Garth Simpson
• 金额: $ 45万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2004046&HistoricalAwards=false
• 关键词: D3SC; Nonlinear; Optical; Analysis; Proteins

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Garth Simpson and his group at Purdue University are devising sophisticated new optical methods and machine learning-based data analysis tools capable of probing the changes of structure and flexibility that occur when proteins transition from solutions to glassy matrices. Some proteins retain function in amorphous glasses, even in the absence of liquid water. This effect enables some living creatures to survive even below the freezing point of water. Glassy matrices can also support long-term storage and delivery of therapeutic proteins - another context in which it is important to understand the properties of proteins in these matrices. The methods being developed by the Simpson group are designed to improve our fundamental understanding of the nature of protein/matrix interactions upon removal of water. Dr. Simpson is communicating the principles behind his research to broad audiences through short instructional videos and through industrial interactions in an NSF Industry/University Collaborative Research Center. The Simpson group is working on three innovative approaches to probing the protein and sugar structural and dynamic changes that accompany the lyophilization-induced transition of sugars from co-solutes in aqueous environments to protein-stabilizing matrices. First, they are developing new Fourier transform methods for substantially improving the information content in fluorescence recovery after photobleaching (FRAP) in order to enable rapid assessment of mobility/relaxation within low volumes (~100 nL) of both aqueous solutions and lyophilized materials. Second, they are devising means of atomic-level mapping of structural evolution within proteins upon water removal using a one-of-a-kind instrument designed and built in collaboration with Argonne National Laboratory. The approach combines nonlinear optical imaging, synchrotron X-ray diffraction, and unique data-handling algorithms based on non-negative matrix factorization. Third, a novel physics-encoded artificial neural network (PENN) is being designed, trained, and tested as a means of gaining improved understanding of the physical origins of observed structure and mobility changes. The long-term aim is to develop experimental/computation methods that can improve fundamental understanding and provide capabilities for predicting the dynamic transformations in proteins within glassy matrices.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.

在化学系化学测量和成像项目的支持下，普渡大学的Garth Simpson教授和他的团队正在设计复杂的新光学方法和基于机器学习的数据分析工具，能够探测蛋白质从溶液转变为玻璃状基质时结构和灵活性的变化。有些蛋白质即使在没有液态水的情况下也能在无定形玻璃中保持功能。这种作用使一些生物即使在水的冰点以下也能生存。玻璃基质还可以支持治疗性蛋白质的长期储存和递送——这是了解这些基质中蛋白质特性的另一个重要背景。辛普森小组正在开发的方法旨在提高我们对去除水后蛋白质/基质相互作用性质的基本理解。在美国国家科学基金会产学研合作研究中心，辛普森博士通过简短的教学视频和行业互动，向广大观众传达了他研究背后的原理。辛普森小组正在研究三种创新的方法来探测蛋白质和糖的结构和动态变化，这些变化伴随着冻干诱导的糖从水环境中的共溶质到蛋白质稳定基质的转变。首先，他们正在开发新的傅立叶变换方法，以大幅提高光漂白后荧光恢复（FRAP）中的信息含量，以便能够在水溶液和冻干材料的低体积（~100 nL）内快速评估迁移率/弛缓性。其次，他们正在设计一种原子水平的方法，利用与阿贡国家实验室合作设计和制造的一种独一无二的仪器，绘制蛋白质在水去除过程中的结构演变图。该方法结合了非线性光学成像、同步加速器x射线衍射和基于非负矩阵分解的独特数据处理算法。第三，一种新的物理编码人工神经网络（PENN）正在被设计、训练和测试，作为一种手段，可以更好地理解观察到的结构和迁移变化的物理起源。长期目标是开发实验/计算方法，以提高基本理解，并提供预测玻璃基质中蛋白质动态转化的能力。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。

项目成果

Theoretical basis for interpreting heterodyne chirality-selective sum frequency generation spectra of water

• DOI: 10.1063/5.0181718
• 发表时间: 2024-02-07
• 期刊: JOURNAL OF CHEMICAL PHYSICS
• 影响因子: 4.4
• 作者: Konstantinovsky，Daniel;Santiago，Ty;Yan，Elsa C. Y.
• 通讯作者: Yan，Elsa C. Y.

Incoherent Nonreciprocal Absorbance Circular Dichroism of Uniaxial Assemblies

• DOI: 10.1021/acs.jpcb.3c03104
• 发表时间: 2023-09-18
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Turner，Gwendylan A.;Hwang，Yechan;Simpson，Garth J.
• 通讯作者: Simpson，Garth J.

Label-Free Autofluorescence-Detected Mid-Infrared Photothermal Microscopy of Pharmaceutical Materials

药物材料的无标记自发荧光检测中红外光热显微镜

• DOI: 10.1021/acs.analchem.1c05504
• 发表时间: 2022
• 期刊: Analytical Chemistry
• 影响因子: 7.4
• 作者: Razumtcev, Aleksandr;Li, Minghe;Rong, Jiayue;Teng, Chu C.;Pfluegl, Christian;Taylor, Lynne S.;Simpson, Garth J.
• 通讯作者: Simpson, Garth J.

Depth-of-field extension in optical imaging for rapid crystal screening

用于快速晶体筛选的光学成像景深扩展

• DOI: 10.1107/s2059798321000097
• 发表时间: 2021
• 期刊: Acta Crystallographica Section D Structural Biology
• 作者: Li, Chen;Ding, Changqin;Li, Minghe;Rong, Jiayue;Florian, Hilary;Simpson, Garth
• 通讯作者: Simpson, Garth

Disparities of Single-Particle Growth Rates in Buried Versus Exposed Ritonavir Crystals within Amorphous Solid Dispersions

• DOI: 10.1021/acs.molpharmaceut.0c00744
• 发表时间: 2020-12-07
• 期刊: MOLECULAR PHARMACEUTICS
• 影响因子: 4.9
• 作者: Griffin, Scott R.;Takanti, Nita;Simpson, Garth J.
• 通讯作者: Simpson, Garth J.