AF: Medium: Collaborative Research: Top-down algorithmic design of structured nucleic acid assemblies

AF：中：协作研究：结构化核酸组装体的自上而下的算法设计

• 批准号: 1564025
• 负责人: Mark Bathe
• 金额: $ 63.85万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1564025&HistoricalAwards=false
• 关键词: AF; Medium; Collaborative; Research; Top; AF; Medium; Collaborative; Research; Top

The past decade has witnessed dramatic growth in ability to "print" complex nanometer-scale structures and patterns using self-assembling nucleic acids. These structures can be used as templates to synthesize inorganic materials on the 1-100 nanometer-scale, or employed directly in applications such as DNA-based memory storage, therapeutic delivery, single-molecule structure-determination, and nanoscale excitonic materials. While various computational strategies are available to forward design these complex 3D structures manually from underlying DNA or RNA sequence and topology, the inverse problem of autonomously generating linear nucleic acid sequences from target geometry alone remains an unsolved computational challenge. In this project, fully automatic, top-down computer-aided design (CAD) algorithms are explored to generate topological sequence designs for broad classes of programmed DNA and RNA assemblies in an autonomous manner using target geometry alone. These assemblies can be "printed" via self-assembly in vitro or in vivo to form target nanoscale geometries using either synthetic or transcribed nucleic acids. The approach will offer a broadly accessible, high-level programming language to realize sequence-based programming of arbitrary 1D/2D/3D nanoscale structured materials based on nucleic acids with diverse applications in basic science and nanotechnology.The proposed computational algorithms will be distributed freely online as open source software as well as integrated into a variety of software packages to broadly enable the top-down design of DNA and RNA assemblies. These algorithms and software will provide the broader scientific and industrial communities with easy-to-use, high-level design strategies that will accelerate the broad participation of groups in the use of nucleic acid nanotechnology for diverse applications in biomolecular and materials science and technology. The tools will open up opportunities for high school students and undergraduates to gain hands-on experience in nucleic acid nanostructure design. Curriculum developments at ASU and MIT will employ the use of this sequence design software for participation by undergraduate and graduate students in its use and application to basic questions in computer science and nanotechnology research.Foundational aspects of the design of nanoscale structured materials using DNA and RNA will be explored. Algorithmic approaches to rendering diverse CAD-based geometric primitives using DNA and RNA will be investigated, including wireframe lattices in 2D and 3D, single-layer surfaces that may contain arbitrary curvatures, as well as 3D solid objects. Meshing algorithms will be used to discretize geometric objects in 1D, 2D, and 3D, and topological routing and sequence design will be applied to position nucleic acid strands within CAD objects. Continuous and discontinuous single stranded nucleic acids will be routed through duplexes using anti-parallel and parallel crossover configurations to exploit distinct modes of programmed self-assembly. Sequence design and routing will be validated experimentally to explore principles for obtaining optimal folding, self-assembly, and positioning of specific base pairs in 3D space. Self-assembly of nanostructures from RNA will additionally be explored, utilizing staple-free designs from single long continuous scaffold strands. Close interaction between experiment and computation will help to distill fundamental yet practical approaches to programming structured nucleic acid assemblies.

过去的十年见证了使用自组装核酸“打印”复杂纳米尺度结构和模式的能力急剧增长。这些结构可以用作模板，以合成1-100纳米尺度上的无机材料，也可以直接在基于DNA的存储器存储，治疗递送，单分子结构确定和纳米级激发型材料等应用中使用。尽管可以从基本的DNA或RNA序列和拓扑中手动设计这些复杂的3D结构来转发各种计算策略，但仅靠目标几何形状自主生成线性核酸序列的反问题仍然是未解决的计算挑战。在此项目中，探索了全自动的，自动自上而下的计算机辅助设计（CAD）算法，以生成拓扑序列设计，以使用单独的目标几何形状以自主的方式为广泛的编程DNA和RNA组件生成拓扑序列设计。这些组件可以通过体外或体内自组装“印刷”，以使用合成或转录的核酸形成目标纳米级的几何形状。该方法将提供一种可广泛的高级编程语言，以实现基于序列的1D/2D/3D纳米级的基于序列的编程，这些纳米级结构化材料基于基础科学和纳米技术的各种应用。拟议的计算算法将自由地在线分配为开源软件，并将其集成到各种软件中，并将其集成为各种装置，并将其分配到广泛的软件中。这些算法和软件将为更广泛的科学和工业社区提供易于使用的高级设计策略，这些策略将加速群体在使用核酸纳米技术在生物分子和材料科学和技术中的多种应用中的广泛参与。这些工具将为高中生和本科生为获得核酸纳米结构设计的动手经验提供机会。 ASU和MIT的课程开发将利用该序列设计软件的本科生和研究生参与其使用，并将其用于计算机科学和纳米技术研究中的基本问题。将探索纳米级设计材料设计的基础化方面，使用DNA和RNA。将研究使用DNA和RNA渲染基于CAD的几何原始素的算法方法，包括2D和3D中的线框晶格，单层表面，可能包含任意曲率，以及3D固体对象。网络算法将用于在1D，2D和3D中离散几何对象，拓扑路由和序列设计将应用于CAD对象中的核酸链位置。连续和不连续的单链核酸将使用反平行和平行的交叉构型通过双链酸来扩展，以利用编程的自组装的不同模式。序列设计和路由将经过实验验证，以探索在3D空间中特定基础对获得最佳折叠，自组装和定位的原理。还将探索来自RNA的纳米结构的自组装，并利用单个长连续脚手架链中的无钉书钉设计。实验和计算之间的紧密相互作用将有助于提炼基本而实用的方法来编程结构化核酸组件。