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

蛋白质提供了一系列非凡的结构、特性和功能，可用于设计和制造新型设备和材料。从长远来看，这项研究对包括人工关节和人工瓣膜在内的植入式医疗器械的发展具有重要意义。这种应用的关键是将蛋白质有效地集成到设备中。为此，人们对将肽和蛋白质可靠地附着在非生物表面和材料上很感兴趣。生物分子与表面之间的界面具有与生物组分和原始表面相关但又截然不同的特性。与表面相连的蛋白质的三维结构和由此产生的功能可能与溶液中的完全不同。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·韦伯博士的研究小组正在利用一个多学科研究项目来解决这些挑战，该项目专注于研究合理设计和精确制备的表面上的生物分子。韦伯博士鼓励高中生在她自己的实验室里参与研究。特别强调的是增加德克萨斯州高中的招生工作，以便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。尽管生物分子与非生物材料的整合是当前科学界感兴趣的一个领域，但对附着在表面的生物分子与溶液中的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多肽和蛋白质等生物分子在这些可选择的底物结合环境中发生的变化缺乏基本理解的问题。Webb博士的实验室正在使用一个独特的化学平台和一套先进的分析工具，从实验和计算的角度来解决这些基本问题。金表面被电子转移蛋白azurin化学功能化，研究蛋白质的功能旨在探索金保持稳定的条件。该研究阐明了表面结合肽链成核和形成原纤维的机制。研究了名义上干燥的表面结合蛋白水合作用对其结构和功能的影响。实验结果被用于开发、测试和验证计算方法，这些计算方法可以准确地预测附着在人工表面的蛋白质和肽的结构。Webb博士的长期目标是推进对表面多肽和蛋白质行为的化学理解，以便与目前可能的溶液相系统相比，这种理解达到类似的准确性和可预测性。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。

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.