Formation, Hydration, and Structure of Biomolecules at the Protein-Surface Interface

蛋白质-表面界面生物分子的形成、水合和结构

• 批准号: 1807215
• 负责人: Lauren Webb
• 金额: $ 44万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807215&HistoricalAwards=false
• 关键词: Formation; Hydration; Structure; Biomolecules; Protein

Proteins provide an extraordinary range of structures, properties, and functions that could be used in the design and building of novel devices and materials. Long term, this research has implications on the development of implantable medical devices including artificial joints and valves. Critical for such applications is for the protein to be effectively integrated into the devices. To this end, there is interest in attaching peptides and proteins to non-biological surfaces and materials reliably. The interface between the biomolecules and surface has properties are related to, but quite distinct from, those of the biological components and of the original surface. The three-dimensional structure and resulting function of proteins linked to surfaces can be radically different than in solution. Defining these differences is challenging. The research group of Dr. Lauren Webb at the University of Texas at Austin is addressing these challenges using a multidisciplinary research program focused on the investigation of biomolecules on rationally-designed and precisely-prepared surfaces. Dr. Webb fosters the participation of high school students in research in her own laboratories. Special emphasis is placed on increasing recruiting efforts in Texas high schools so that the diversity of students engaged in research reflects the diversity of the population of Texas. Despite the fact that the integration of biological molecules with non-biological materials is an area of current scientific interest, the understanding of the differences between the structures and properties of biomolecules attached to surfaces versus biomolecules in solution is relatively limited. Dr. Webb's research addresses the lack of fundamental understanding of what happens to biomolecules such as peptides and proteins in these alternative, substrate-bound environments. Dr. Webb's laboratory is using a unique chemical platform and an advanced set of analytical tools to address these fundamental questions from both an experimental and computational perspective. Gold surfaces are chemically functionalized with the electron-transfer protein azurin and studies of the protein's function are aimed at exploring conditions under which the gold remains stable. The research elucidates the mechanism of nucleation and formation of fibrils from surface-bound strand peptides. It also examines the influence of hydration of nominally dry surface-bound protein on the protein's structure and function. The experimental results are leveraged towards the development, testing, and validation of computational methods that may accurately predict the structure of proteins and peptides attached to artificial surfaces. Dr. Webb's long-term goal is to advance of the chemical understanding of peptides and protein behavior at surfaces so that the understanding reaches similar accuracy and predictability when compared to what is currently possible for solution-phase systems.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.

蛋白质提供了可用于新型设备和材料的设计和建造的非凡结构，特性和功能。从长远来看，这项研究对包括人造关节和阀门在内的可植入医疗设备的开发具有影响。对于这种应用至关重要的是，要使蛋白质有效地整合到设备中。为此，有兴趣将肽和蛋白质附加到非生物表面和材料上。生物分子和表面之间的界面具有特性与生物成分和原始表面的界面有关。链接到表面的蛋白质的三维结构和产生的功能可能与溶液完全不同。 定义这些差异是具有挑战性的。德克萨斯大学奥斯汀分校的劳伦·韦伯（Lauren Webb）的研究小组正在使用一项多学科研究计划来应对这些挑战，该计划的重点是研究生物分子对合理设计的和精确的表面。韦伯博士促进了高中生在自己的实验室中研究的参与。特别重点是增加得克萨斯州高中的招聘工作，因此从事研究的学生的多样性反映了德克萨斯州人口的多样性。尽管事实是，生物分子与非生物学材料的整合是当前科学意义的领域，但对溶液中与表面相对于生物分子的结构和性质之间的差异的理解相对有限。 Webb博士的研究解决了对这些替代性底物环境中肽和蛋白质等生物分子发生的情况的基本了解。 Webb博士的实验室正在使用独特的化学平台和一组先进的分析工具来从实验和计算的角度解决这些基本问题。金表面用电子转移蛋白蓝蛋白化学功能化，对蛋白质功能的研究旨在探索金稳定的条件。该研究阐明了成核的机理和从表面结合的链肽形成原纤维的机制。它还研究了名义干燥的表面结合蛋白对蛋白质结构和功能的水合的影响。实验结果将用于开发，测试和验证计算方法，这些计算方法可以准确预测附着在人造表面上的蛋白质和肽的结构。韦伯博士的长期目标是提高对肽和蛋白质行为的化学理解，以便与解决方案相系统相比，理解具有相似的准确性和可预测性。该奖项反映了NSF的法定任务和使用基金会的知识分子优点和更广泛的审查标准，通过评估被认为值得支持。

项目成果

Cross-Seeding Controls Aβ Fibril Populations and Resulting Functions

• DOI: 10.1021/acs.jpcb.1c09995
• 发表时间: 2022-03-24
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Lucas, Michael J.;Pan, Henry S.;Webb, Lauren J.
• 通讯作者: Webb, Lauren J.

Structural Evaluation of Protein/Metal Complexes via Native Electrospray Ultraviolet Photodissociation Mass Spectrometry

• DOI: 10.1021/jasms.0c00066
• 发表时间: 2020-05-06
• 期刊: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
• 影响因子: 3.2
• 作者: Crittenden, Christopher M.;Novelli, Elisa T.;Brodbelt, Jennifer S.
• 通讯作者: Brodbelt, Jennifer S.

Functionalized Mesoporous Silicas Direct Structural Polymorphism of Amyloid-β Fibrils

功能化介孔二氧化硅淀粉样蛋白-β原纤维的直接结构多态性

• DOI: 10.1021/acs.langmuir.0c00827
• 发表时间: 2020
• 期刊: Langmuir
• 影响因子: 3.9
• 作者: Lucas, Michael J.;Pan, Henry S.;Verbeke, Eric J.;Webb, Lauren J.;Taylor, David W.;Keitz, Benjamin K.
• 通讯作者: Keitz, Benjamin K.

Characterizing protein–surface and protein–nanoparticle conjugates: Activity, binding, and structure

表征蛋白质-表面和蛋白质-纳米颗粒缀合物：活性、结合和结构

• DOI: 10.1063/5.0101406
• 发表时间: 2022
• 期刊: The Journal of Chemical Physics
• 作者: Correira, Joshua M.;Handali, Paul R.;Webb, Lauren J.
• 通讯作者: Webb, Lauren J.

Agreement between Experimental and Simulated Circular Dichroic Spectra of a Positively Charged Peptide in Aqueous Solution and on Self-Assembled Monolayers

带正电荷的肽在水溶液中和自组装单分子层上的实验和模拟圆二色光谱之间的一致性

• DOI: 10.1021/acs.jpcb.9b02102
• 发表时间: 2019
• 期刊: The Journal of Physical Chemistry B
• 作者: First, Jeremy T.;Webb, Lauren J.
• 通讯作者: Webb, Lauren J.