CAREER: Programmable Assembly of Glycine-Rich Peptides on a Graphitic Surface

非技术总结这个职业奖项支持理论研究、计算机模拟和验证性实验，以设计可以通过编程将自己排列成复杂设备的分子。一部可以装在口袋里的现代智能手机比20年前的一台笨重的笔记本电脑具有更强的计算能力，同时还包括数码相机、GPS和拨打无线电话的能力。设备的小型化已经如此成功，以至于一些组件的大小正在增长到接近分子和原子的大小，这需要对设备的构建方式进行重大改变。建造沙堡似乎已经让位于用单独的沙粒建造微小的城堡。虽然用单个分子制造设备可能很困难，但它是可以做到的；生物以单原子的精度制造数千种不同的蛋白质，每个蛋白质都执行不同的功能，同时往往会将自己排列成更大、更复杂的结构。这个项目的目标是设计类似蛋白质的分子，这些分子也能够类似地自我排列，但方式可以很容易地由人类工程师编程。为了使设备的成像和设计变得更容易，该项目的重点是在原子平坦的石墨烯表面上排列自己的分子。研究小组将使用计算机模拟来优化对安排的控制，对照实验检查计算机预测。这项研究应该会为用单分子设计未来的设备揭示新的理论原理。此外，分子的生物学性质意味着它们可能被应用于医学应用。本科生和研究生，包括那些在科学研究中被低估的少数群体，将参与其中，学习尖端的计算技术。研究小组还寻求开发用于大学课堂和K-12推广的分子的计算机模拟，让学生看到分子是如何运动的，并让他们感受世界是如何在这个微小的水平上运行的。互动模拟将包括那些旨在帮助学生了解药物如何起作用以及如何设计新药的模拟。教育模块和模拟程序将免费提供给教育工作者和公众，并将包括英语和西班牙语版本。TECHNICAL SUMMARY这个职业奖项支持研究，以解决工程自组装结构中的一个基本问题：如何设计既具有采用任意有用结构的灵活性，又具有采用高保真的独特编程结构的选择性的分子元件。该项目的目标是开发一个理论框架和计算工具，用于设计可编程汇编的构建块。该项目的重点是富含甘氨酸的多肽，这些多肽在石墨表面折叠成独特的构象，并以可预测的方式自组装。这种多肽-石墨烯体系似乎是创造可编程材料的最佳选择，因为有效的二维结构简化了成像，减少了多肽的构象和构象自由度，有利于有序结构，便于理论分析和分子动力学模拟。研究小组将使用分子动力学模拟和最先进的自由能计算技术来筛选大量的多肽序列，以找到适合可编程组装的元件集。计算预测将用原子力和电子显微镜进行实验验证。该项目的结果有望通过建立理论和计算工具来为纳米设备的可编程组装找到具有最佳相互作用热力学的分子基序集，从而推动分子自组装领域的发展。该项目将包括开发新的算法和免费提供的软件，用于增强采样、自由能计算和交互分子设计，可能会推动分子模拟领域的发展。该职业奖还支持与研究领域相关的教育活动。该团队还将利用易于使用的基于浏览器的模拟来创建互动教育模块，这些模块将根据药物设计研究生课程、热力学本科课程和K-12推广活动而量身定做。这些单元将包括英语和西班牙语版本。参与这项研究的研究生和本科生，包括一些来自历史上在科学和技术领域代表性不足的人群，将接触到纳米科学和先进的计算技术。该项目由材料研究部的凝聚态物质和材料理论计划和既定的刺激竞争研究计划(EPSCoR)联合资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

NONTECHNICAL SUMMARYThis CAREER award supports theoretical research, computer simulations, and validating experiments to design molecules that can be programmed to arrange themselves into complex devices. A modern smartphone that fits in a pocket has more computing power than a hefty laptop of 20 years ago, while also including a digital camera, GPS, and the ability to make wireless calls. The miniaturization of devices has been so successful that the size of some components is growing close to the size of molecules and atoms, requiring big changes in how devices are built. It is as if building sandcastles has given way to building tiny castles out of individual grains of sand. While making devices from individual molecules may be difficult, it can be done; living things make thousands of different proteins with single-atom precision, each performing a different function while often arranging themselves into larger, more complex structures.The goal of this project is to design protein-like molecules that are similarly able to arrange themselves, but in a way that can be easily programmed by a human engineer. To make imaging and design of the devices easier, the project is focused on molecules that arrange themselves on top of an atomically flat graphene surface. The research team will use computer simulations to optimize control over the arrangement, checking the computer predictions against experiments. This research should reveal new theoretical principles for designing future devices from single molecules. Also, the biological nature of the molecules means that they might be applied in medical applications. Undergraduate and graduate students, including those from minority groups underrepresented in scientific research, will participate, learning cutting-edge computational techniques.The research team also seeks to develop computer simulations of molecules for use in college classrooms and in K-12 outreach, letting students see how molecules move and giving them a feel for how the world works at this tiny level. The interactive simulations will include those aimed at helping students understand how medicines work and how new medicines can be designed. The educational modules and simulation programs will be made freely available to educators and the public, and will include English- and Spanish-language versions.TECHNICAL SUMMARYThis CAREER award supports research to address a fundamental problem in engineering self-assembled structures: how to design molecular elements that possess both the flexibility to adopt arbitrary useful structures and the selectivity to adopt a unique programmed structure with high fidelity. The goal of the project is to develop a theoretical framework and computational tools for designing building blocks for programmable assembly. The project is focused on glycine-rich peptides that fold into unique conformations on graphitic surfaces and self-assemble in predictable ways. This peptide-graphene system seems optimal for creation of programmable materials because the effectively two-dimensional architecture simplifies imaging and reduces the peptides' conformational and configurational freedom, favoring ordered structures and facilitating analysis by theory and molecular dynamics simulation.The research team will use molecular dynamics simulations and state-of-the-art free-energy calculation techniques to screen large numbers of peptide sequences to find sets of elements suitable for programmable assembly. The computational predictions will be experimentally validated using atomic force and electron microscopy. The results of this project are anticipated to advance the field of molecular self-assembly by establishing theoretical and computational tools to find sets of molecular motifs with optimal interaction thermodynamics for programmable assembly of nanodevices. The project will involve the development of new algorithms and freely available software for enhanced sampling, free-energy calculation, and interactive molecular design, likely advancing the field of molecular simulation.This CAREER award also supports education activities related to the research area. The team will also create interactive educational modules leveraging easy-to-use browser-based simulations, which will be tailored to a graduate course on drug design, undergraduate courses on thermodynamics, and K-12 outreach activities. These modules will include English- and Spanish-language versions. Graduate and undergraduate students participating in the research, including some from populations historically underrepresented in science and technology fields, will gain exposure to nanoscience and advanced computational techniques.This project is jointly funded by the Condensed-Matter-and-Materials-Theory program in the Division of Materials Research and by the Established Program to Stimulate Competitive Research (EPSCoR).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.