A Shape Annealing Approach to DNA Origami Design

该项目的目标是利用DNA（生命的基石）自动设计纳米级生物力学结构。这些设备可用于制造纳米机器、传感器和纳米机器人，用于从生物物理学到物理计算的各个领域。这些设计需要构建长链DNA，这些DNA以某种方式连接在一起，以提供形状和结构完整性。尽管计算机辅助设计（CAD）工具已经存在，可以帮助设计师将这些钢索放置到可用的配置中，并确定钢索连接在一起的位置，但设计师必须首先充分构思结构的整体设计；CAD工具是用来填充细节的，但不能自己生成设计布局和特征。这项研究旨在改变DNA纳米结构（也被称为“DNA折纸”，因为它们折叠和连接在一起的方式）从自动化概念生成到布局到制造的设计方式。由此产生的设计工具将免费提供，这将使DNA纳米技术和设计界能够自动生成在形式和功能上都得到优化的纳米结构设计，并使生物传感、制造和机器人领域的更广泛的研究人员能够将DNA折纸应用于他们的研究领域。这项工作拓宽了设计研究的进展到一个新的应用领域，寻求效率和设计创新。此外，这项工作将导致新的教育努力，包括虚拟DNA折纸实验室之旅。从技术上讲，这项工作将通过基于形状的生产语法和随机搜索（一种称为形状退火的方法）来合并DNA折纸结构及其布局的自下而上设计的自动设计搜索。形状语法能够表示可行和首选的DNA组合，并将基于DNA链及其组合的物理特性构建；模拟退火允许最优或首选顺序构建完整的DNA折纸结构。我们将探索一种多层形状语法方法，从宏观结构开始，然后通过低级语法提炼出详细的特征。提供对设计质量和进展的实时反馈，分析也将是多层次的，并利用模拟退火从几乎随机到确定性的进展，与预训练的基于物理的性能模拟过渡到粗粒度分子动力学模拟，然后到全原子模拟。解决方案将与当前的DNA折纸CAD工具（如caDNAno）兼容，并通过湿实验室的制造进行验证。该奖项反映了美国国家科学基金会的法定使命，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。

The goal of this project is to automate the design of nano-sized biomechanical structures using DNA, the building block of life. These devices can be used to manufacture nanomachines, sensors, and nanorobots for use in fields ranging from biophysics to physical computing. These designs require the building of long strands of DNA that are joined in ways to provide shape and structural integrity. Although computer aided design (CAD) tools exist to help the designer to place these strands into usable configurations and determine locations to join strands together, the designer must first fully conceive of the overall design of the structure; the CAD tools are there to fill in the detail but not generate the design layout and features themselves. This research seeks to change the way DNA nanostructures (also called “DNA origami” because of the way they are folded and joined together) are designed from automated concept generation to layout to manufacture. Resulting design tools, to be made freely available, will enable the DNA nanotechnology and design communities to automatically generate nanostructure designs that are optimized for both form and function, and enable a broader audience of researchers in biosensing, manufacturing and robotics to apply DNA origami to their fields of study. This work broadens the advancement of design research to a new field of application, seeking efficiency and design innovation. In addition, this work will lead to new educational endeavors, including a virtual DNA origami lab tour.Technically, this work will merge automated design search through shape-based production grammars and stochastic search (a method called shape annealing) for the bottom-up design of DNA origami structures and their layouts. Shape grammars enable the representation of feasible and preferred DNA combinations and will be built based on the physical properties of DNA strands and their combination; simulated annealing allows for the optimal or preferred sequential build of complete DNA origami structures. A multi-tiered shape grammar approach will be explored that begins with a macro structure and then refines the detailed features through a lower-level grammar. Providing real time feedback on the quality and progress of the design, analysis will also be multi-tiered and leverage the progression of simulated annealing from nearly random to deterministic, with pre-trained physics-based performance simulation transitioning to coarse grained molecular dynamics simulation and then to all-atom simulation. Solutions will be compatible with current DNA origami CAD tools such as caDNAno and verified through manufacture in the wet lab.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.