CAREER: Design and modeling for modular bionanotechnology and citizen science

非技术性SUMMARYBIONANO技术是一个使用设计的分子在纳米级构建设备和结构的领域，在开发新材料、检测设备以及治疗或诊断平台方面具有广阔的应用前景。然而，这种装置的建造带来了巨大的技术挑战。计算机建模可以为此类系统的设计机制提供有用的见解。在我们的宏观世界中，经常使用计算机辅助设计软件来设计计算机芯片、汽车、飞机等，以便首先在模拟中测试和优化设备的操作。然而，纳米级的建造带来了多重挑战。与我们的宏观世界不同，纳米结构通常是通过自组装实现的，即单个组件随机扩散，直到它们相遇并组装成目标结构。为了实现更复杂的高产率自组装结构，需要一种新的模拟框架，能够有效地同时准确地表示这种纳米结构的组装和功能。该项目将开发一种新的建模框架，能够模拟自组装的DNA纳米结构，这是目前生物纳米技术中最先进的分支之一。研究团队将使用这个框架来优化纳米结构的组装，以获得高产量，并通过计算设计新型的可重构纳米结构。接下来，该团队将扩展建模平台，以允许合并其他有机/无机分子和材料，并使用它来设计一种可以在一个方向上优先移动的纳米微米。总体而言，该项目将促进新纳米设备的创建，这些设备能够执行复杂的任务，如果没有复杂的建模平台，这些任务将很难在实验中实现，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普通民众开发新的学习机会。主要工作将包括开发一个在线公民科学平台，用户可以在其中使用模拟平台自己设计和优化结构，从而允许众包纳米技术设计。技术综述：核酸纳米技术是生物纳米技术中最先进的分支之一，具有从生物模板化制造到诊断和治疗的广泛应用前景。然而，系统的大小(数千个核苷酸)和与它们的组装和功能相关的时间尺度(几分钟到几个小时)使得它们的组装动力学模型非常具有挑战性。因此，该领域迫切需要计算建模工具，这些工具可以将更多的分子和材料合并到DNA或RNA纳米结构中，模拟远离平衡的过程，如ATP驱动的马达，并在长时间的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纳米结构的组装动力学，并优化它们的设计以提高产量。PI将使用这个框架来设计新型的DNA和RNA纳米结构，这些结构具有可控的折叠路径，专门选择一种可能的稳定分子构象，从而创造出一种可重新配置的生物材料。接下来，研究团队将使用建模平台来设计一种能够定向移动的由ATP驱动的纳米吸入器。在这个项目中开发的总体框架将允许模块化设计，并利用不同的材料(有机和无机)和功能分子络合物来构建纳米技术，从而使纳米技术领域更接近行业规模的应用，并将理论建模纳入生物纳米技术设计流水线。作为教学计划的一部分，PI的教育计划将专注于培训本科生和研究生解决生物纳米技术问题所需的跨学科研究技能，并创造实际动手研究机会。此外，该项目还将开发公民科学在线平台。该平台将使用一个类似游戏的界面，玩家将在其中解决设计功能性DNA纳米结构的真正科学问题，这些问题将使用开发的计算机模型进行测试。这一奖项反映了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 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.