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

#1512058霍尔，卡罗尔K。能够在水中或高湿度条件下粘附到表面的通用粘合剂在从船舶涂料到医疗设备到水下传感器的应用中具有需求。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的因素，这两个因素似乎有助于它们在水中附着到广泛表面的能力：3，4-二羟基苯丙氨酸（DOPA）和淀粉样蛋白形成肽。通过将合成的含DOPA的聚合物和淀粉样蛋白形成肽相结合，将开发出一类新的通用水下粘合剂。将使用合成材料，而不是其他研究人员青睐的天然蛋白质，因为它们应该更容易定制和大规模生产。将进行计算驱动的研究程序，以更好地理解肽-聚合物缀合物中的肽序列和含DOPA的聚合物如何被工程化以协同作用，从而提供对水中表面的上级粘附。原子和粗粒度的分子模拟将用于开发一套分子水平的原则，可以指导多巴-肽缀合物的设计。这些材料受到包括贻贝和藤壶在内的天然材料的启发，预计将成为新一代水下粘合剂的基础，能够粘合到各种表面。从酵母细胞所用的胶的淀粉样蛋白形成区域中提取的五个短肽序列已被鉴定为良好的起始序列。将考虑四种表面：石墨、涂覆有OH基团的石墨、金和氧化钛。本课题的具体目标是：1）确定天然肽上每个氨基酸残基在形成淀粉样结构中所起的作用; 2）开发一套设计聚合物-肽缀合物的原则，使肽可以在不与聚合物缔合的情况下形成淀粉样结构;和3）研究四个模型表面附近缀合物的行为，以评估它们在水中非特异性附着的能力。最有希望的DOPA-肽缀合物将由实验合作者合成，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，其中材料在水中粘附到表面是至关重要的。计算设计策略从天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，以找到有前途的分子结构，可以为系统设计和发现其他新材料指明方向。 除了培养博士学位外，将通过以下方式促进学生、研究和教育：（1）使用新材料的计算设计作为PI的本科化学工程热力学课程开发的示例的基础，（2）创建描述计算材料设计的基础知识并通过网络分发的powerpoint演示文稿，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将继续开展大量但非正式的全国性活动，以扩大妇女在STEM领域的机会，并将为NCSU她所在部门的女研究生和博士后介绍一系列棕色午餐，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.