UNS: Computational Design of Generic Underwater Adhesives based on Conjugating DOPA-Containing Polymers and Amyloid-Forming Peptides

#1512058Hall, Carol K.能够在水中或高湿度条件下粘附表面的通用粘合剂需求广泛，应用范围从船舶涂料到医疗设备到水下传感器。开发这种粘合剂的一种方法是向大自然学习。对贻贝、藤壶、藻类和酵母所使用的粘附物质的分析揭示了两个共同因素，它们似乎有助于它们附着在水中各种表面：3,4 -二羟基苯丙氨酸（DOPA）和淀粉样蛋白形成肽。将合成含多巴的聚合物与淀粉样蛋白形成肽相结合，开发出一类新型的通用水下胶粘剂。他们将使用合成材料，而不是其他研究者青睐的天然蛋白质，因为它们更容易定制和大规模生产。将进行一个计算驱动的研究项目，以更好地了解肽-聚合物缀合物中肽序列和含多巴的聚合物如何被设计成协同作用，从而在水中提供优越的表面粘附。原子和粗粒度分子模拟将用于开发一套分子水平的原则，可以指导多巴肽偶联物的设计。这种材料的灵感来自于自然产生的材料，包括贻贝和藤壶，有望形成新一代水下粘合剂的基础，能够结合到各种表面。从酵母细胞使用的淀粉样蛋白形成区域提取的五个短肽序列已被确定为良好的起始序列。将考虑四种表面：石墨、涂有羟基的石墨、金和氧化钛。该项目的具体目标是：1)确定天然衍生肽上每个氨基酸残基在形成淀粉样蛋白结构中的作用；2)开发一套设计聚合物-肽偶联物的原则，使肽可以在不与聚合物结合的情况下形成淀粉样结构；3)研究共轭物在四个模型表面附近的行为，以评估它们在水中非特异性附着的能力。最有希望的多巴肽缀合物将由一位实验合作者合成，并测试它们是否形成淀粉样结构，以及它们是否牢固地粘附在四个表面上。拟议的项目可能会影响界面现象、传感、涂层、表面改性和药物输送等领域的研究，这些领域的材料粘附在水中的表面是至关重要的。计算设计策略从自然产物中获得最初的灵感，然后在原子和粗粒度模拟之间来回迭代，以瞄准有前途的分子结构，这可能为系统设计和发现其他为特定应用量身定制的新材料指明道路。除了培养博士研究生外，研究和教育还将受到以下方面的促进：(1)使用新材料的计算设计作为PI本科化学工程热力学课程开发示例的基础，(2)创建描述计算材料设计基础并通过网络分发的幻灯片演示，以及(3)制作针对普通观众的视频演示，展示如何使用分子水平的计算机模拟来设计具有特殊功能的材料。PI将继续开展其规模可观但非正式的全国性活动，以扩大女性在STEM领域的机会，并将为她所在的北卡州立大学的女性研究生和博士后推出棕色包午餐系列，讨论共同感兴趣的话题。

#1512058Hall, Carol K. Generic adhesives capable of sticking to surfaces in water or in high moisture conditions are in demand for applications ranging from marine coatings to medical devices to underwater sensors. One way to develop such adhesives is to learn from nature. Analysis of the adhesive substances employed by mussels, barnacles, algae and yeasts reveals two common factors that seem to contribute to their ability to attach to a wide range of surfaces in water: 3, 4-dihydroxyphenylalanine (DOPA) and amyloid-forming peptides. A new class of generic underwater adhesives will be developed by combining synthetic DOPA-containing polymers and amyloid-forming peptides. Synthetic materials will be deployed, instead of the naturally-occurring proteins favored by other investigators, because they should be easier to tailor and to produce in large scale. A computationally-driven program of research will be conducted to better the understanding of how the peptide sequences and DOPA-containing polymers in a peptide-polymer conjugate can be engineered to function synergistically, thereby providing superior adhesion to surfaces in water. Atomistic and coarse-grained molecular simulations will be used to develop a set of molecular-level principles that can guide the design of DOPA-peptide conjugates. Such materials, which are inspired by naturally-occurring materials including mussels and barnacles, are expected to form the basis of a new generation of underwater adhesives capable of binding to a wide range of surfaces. Five short peptide sequences taken from the amyloid forming regions of the glues employed by yeast cells have been identified as good starting sequences. Four surfaces will be considered: graphite, graphite coated with OH groups, gold, and titanium oxide. The specific aims of this project are to: 1) identify the roles played by each amino-acid residue on naturally-derived peptides in forming amyloid structure; 2) develop a set of principles for designing polymer-peptide conjugates such that the peptides can form amyloid structures without associating with the polymers; and 3) investigate the behavior of conjugates near four model surfaces to assess their ability to attach nonspecifically in water. The DOPA-peptide conjugates that show the most promise will be synthesized by an experimentalist collaborator, and tested to see if they form amyloid structures and if they adhere strongly to the four surfaces. The proposed project could impact research in the areas of interfacial phenomena, sensing, coating, surface modification and drug delivery where material adherence to surfaces in water is critical. The computational design strategy, which draws initial inspiration from natural products and then iterates back and forth between atomistic and coarse-grained simulations to home in on promising molecular architectures, could point the way to the systematic design and discovery of other new materials that are tailored for specific applications. In addition to training a Ph.D. student, research and education will be fostered by: (1) using the computational design of the new materials as the basis for examples developed for the PI's undergraduate chemical engineering thermodynamics course, (2) creating a power-point presentation describing the basics of computational materials design and distributing via the web, and (3) making a video presentation targeted for general audiences that shows how molecular-level computer simulation can be used to design materials with special functionality. The PI will continue her considerable, but informal, nationwide activities to broaden the opportunities for women in STEM fields and will introduce a brown bag lunch series for women graduate students and postdocs in her department at NCSU to discuss topics of common interest.