CAREER: Design and modeling for modular bionanotechnology and citizen science

非技术概述生物纳米技术是一个使用设计的分子在纳米级水平上构建设备和结构的领域，具有开发新材料，检测设备以及治疗或诊断平台的前景。然而，这种装置的构造提出了重大的技术挑战。计算机建模可以为此类系统的设计机制提供有用的见解。计算机辅助设计软件通常用于我们的宏观世界中，以设计例如计算机芯片、汽车、飞机等，使得可以首先在模拟中测试和优化设备操作。然而，纳米级的构建提出了多种挑战。与我们的宏观世界相反，纳米结构通常是通过自组装实现的，其中各个组件随机扩散，直到它们相遇并组装成目标结构。为了实现更复杂的结构，将自组装在高产量，有一个新的模拟框架，可以有效地，并在同一时间，准确地表示这种纳米结构的组装和功能的需要。该项目将开发一种新的建模框架，能够模拟自组装DNA纳米结构，这是目前生物纳米技术最先进的分支之一。该研究小组将使用该框架来优化纳米结构组装以获得高产量，并通过计算设计新型可重构纳米结构。接下来，该团队将扩展建模平台，以允许纳入其他有机/无机分子和材料，并使用它来设计一种可以优先沿一个方向移动的纳米游泳者。总的来说，该项目将促进创建能够执行复杂任务的新纳米器件，这些任务在没有复杂建模平台的情况下很难通过实验实现，并使该领域更接近大规模工业应用。在项目的教育部分，研究小组将为大学生和公众开发新的学习机会。主要工作将涉及开发一个在线公民科学平台，用户可以使用模拟平台自行设计和优化结构，从而实现众包纳米技术设计。核酸纳米技术是生物纳米技术中最先进的分支之一，具有从生物模板制造到诊断和治疗的广泛应用。然而，系统的大小（数千个核苷酸）和与其组装和功能相关的时间尺度（几分钟到几小时）使其组装动力学非常难以建模。因此，该领域迫切需要计算建模工具，其可以将额外的分子和材料并入DNA或RNA纳米结构中，模拟远离平衡的过程，例如ATP动力马达，并在长实验时间尺度上捕获纳米结构的组装和功能。为了应对这一挑战，该项目将开发一系列新的粗粒度模型，可以模拟大规模的纳米系统，使用它们来研究DNA和RNA纳米结构组装动力学，并优化它们的设计以提高产量。PI将使用这个框架来设计具有受控折叠途径的新型DNA和RNA纳米结构，这些途径专门选择一种可能的分子稳定构象，从而创造出可重构的生物材料。接下来，研究团队将利用建模平台设计一种能够定向运动的ATP动力纳米游泳者，该项目开发的通用框架将允许模块化设计，并利用不同的材料（有机和无机）和功能性分子复合物用于纳米技术构建，从而使纳米技术领域更接近工业-PI的教育计划将侧重于培养本科生和研究生在解决生物纳米技术问题所需的跨学科研究技能利用来自不同领域的方法，并创造实际动手研究的机会，作为教学计划的一部分。此外，该项目还将开发一个公民科学在线平台。该平台将使用类似游戏的界面，玩家将解决设计功能性DNA纳米结构的真实的科学问题，这些问题将使用开发的计算机模型进行测试。该奖项反映了NSF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。

NONTECHNICAL SUMMARYBionanotechnology is a field that uses designed molecules to construct devices and structures at nanoscale level, with promising applications for the development of novel materials, detection devices, as well as platforms for therapeutics or diagnostics. However, construction of such devices presents significant technical challenges. Computer modeling can provide useful insights into the design mechanisms of such systems. Computer-aided design software is often used in our macroscale world to design e.g. computer chips, cars, planes, etc. so that the device operation can be tested and optimized in simulation first. Construction at the nanoscale however presents multiple challenges. As opposed to our macroworld, nanostructures are typically realized by self-assembly, where individual components randomly diffuse until they meet and assemble into a target structure. To realize more complex structures that would self-assemble in high yields, there is a need for a new simulation framework that can efficiently and, at the same time, accurately represent the assembly and function of such nanostructures. This project will develop a new modeling framework that is capable of simulating self-assembled DNA nanostructures, which currently represent one of the most advanced branches of bionanotechnology. The research team will use this framework to optimize nanostructure assembly for high yield, and computationally design new types of reconfigurable nanostructures. Next, the team will extend the modeling platform to allow for the incorporation of other organic/inorganic molecules and materials, and use it to design a nanoswimmer that can move preferentially in one direction. Overall, this project will facilitate the creation of new nanodevices capable of performing complex tasks that would be difficult to realize experimentally without a sophisticated modeling platform, and bring the field closer to large-scale industrial applications. For the education component of the project, the research team will develop new learning opportunities for university students and the general public. The main effort will involve developing an online citizen science platform, where users can use the simulation platform to design and optimize structures themselves, allowing to crowd-source nanotechnology designs. TECHNICAL SUMMARY:Nucleic acid nanotechnology is one of the most advanced branches of bionanotechnology, with promising applications ranging from biotemplated manufacturing to diagnostics and therapeutics. However, the system sizes (thousands of nucleotides) and the timescales associated with their assembly and function (minutes to hours) make their assembly kinetics very challenging to model. There is hence a pressing need in the field for computational modeling tools that can incorporate additional molecules and materials into the DNA or RNA nanostructures, simulate far-from-equilibrium processes such as ATP-powered motors, and capture nanostructures’ assembly and function over long experimental timescales. To address this challenge, this project will develop a new family of coarse-grained models that can simulate large scale nanosystems, use them to study DNA and RNA nanostructure assembly kinetics, and optimize their designs to improve yields. The PI will use this framework to design new types of DNA and RNA nanostructures with controlled folding pathways that specifically select one possible stable conformation of the molecule, thus creating a reconfigurable biomaterial. Next, the research team will use the modeling platform to design an ATP-powered nanoswimmer that is capable of directional motion.The general framework developed in this project will allow modular design and harness different materials (both organic and inorganic) and functional molecular complexes for nanotechnology construction, thus bringing the field of nanotechnology closer to industry-scale applications and incorporating theoretical modeling into the bionanotechnology design pipeline.The PI’s education program will focus on training undergraduate and graduate students in interdisciplinary research skills required to tackle problems in bionanotechnology harnessing approaches from diverse fields and creating practical hands-on research opportunities as part of the teaching program. Furthermore, this project will develop a citizen science online platform. The platform will use a game-like interface where the players will solve real scientific problems of designing functional DNA nanostructures that will be tested using the developed computer models. It will enable crowd-sourcing the design of nanostructures and hence provide a platform to engage the general public in nanotechnology research.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.