A Shape Annealing Approach to DNA Origami Design

该项目的目标是利用DNA这一生命的组成部分，自动设计纳米尺寸的生物力学结构。这些设备可以用来制造纳米机器、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。这些设计需要建造长长的DNA链，这些DNA链以提供形状和结构完整性的方式连接在一起。虽然计算机辅助设计(CAD)工具可以帮助设计者将这些绞线放置到可用的配置中，并确定将绞线连接在一起的位置，但设计师必须首先完全构思结构的整体设计；CAD工具在那里是为了填充细节，而不是生成设计布局和特征本身。这项研究试图改变DNA纳米结构(也被称为DNA折纸，因为它们被折叠和连接在一起的方式)的设计方式，从自动概念生成到布局再到制造。由此产生的设计工具将免费提供，将使DNA纳米技术和设计界能够自动生成针对形式和功能进行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折纸应用到他们的研究领域。这项工作将设计研究的进步拓展到一个新的应用领域，追求效率和设计创新。此外，这项工作将带来新的教育努力，包括虚拟DNA折纸实验室之旅。在技术上，这项工作将结合基于形状的生产语法的自动设计搜索和用于DNA折纸结构及其布局的自下而上设计的随机搜索(一种称为形状退火法)。形状语法能够表示可行的和首选的DNA组合，并且将基于DNA链及其组合的物理性质来构建；模拟退火法允许以最优或首选的顺序构建完整的DNA折纸结构。将探索一种多层形状语法方法，该方法从宏观结构开始，然后通过较低级别的语法细化细节特征。通过提供关于设计质量和进度的实时反馈，分析也将是多层次的，并利用模拟退火法从近乎随机到确定性的进展，通过预先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，然后过渡到全原子模拟。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NSF的法定使命，并已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。

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.