NUPACK: New Capabilities for Nucleic Acid Analysis and Design

在化学系的化学理论、模型和计算方法项目的支持下，奈尔斯A.加州理工学院（Caltech）的皮尔斯将开发用于核酸分析和设计的新算法。核酸（DNA和RNA）通过在复杂的生物回路中相互作用来协调生命，以生长，调节和修复生物体。在未来几十年中，分子编程、核酸纳米技术和合成生物学等新兴领域的DNA和RNA工程有望产生变革性的可编程分子和细胞技术，以应对科学和社会面临的各种挑战，从环境监测和生物圈工程到诊断和治疗，从可再生能源到可持续制造。为了支持这些工程工作，加州理工学院的皮尔斯实验室正在进行数十年的努力，以开发NUPACK（核酸包），这是一种不断发展的软件套件，用于分析和设计核酸结构，设备和系统。在这里，他们将通过追求三个主要目标来扩展NUPACK的能力。首先，他们的目标是开发算法，使模拟功能核酸系统与移动部件。其次，他们将开发分析和设计算法，使处理系统包含混合材料（例如，DNA和RNA，或DNA和合成的核酸类似物如LNA），其对于现代应用是至关重要的，无论是在活生物体中、在实验室工作台上还是在野外。第三，他们将奋进推广NUPACK云Web应用程序，使用户能够有效地利用这些独特的计算工具进行研究和教育。 NUPACK是一个不断发展的软件套件，用于分析和设计核酸结构，设备和系统，满足分子编程，核酸纳米技术，合成生物学和整个生命科学新兴学科研究人员的需求。NUPACK算法在处理包含任意数量的相互作用链物种的复杂和试管集合方面是独一无二的，为捕获分析和设计分子间相互作用所必需的浓度效应提供了关键工具，这些相互作用是这些领域的标志。在这里，加州理工学院的皮尔斯实验室提出通过追求三个主要目标来显着扩展NUPACK的能力。首先，为了能够模拟具有移动部件的功能性核酸系统，他们将开发自动化动力学粗粒化算法，以实现复杂和试管集合的动力学分析。第二，为了实现混合材料系统的工程设计（例如，DNA/RNA或LNA/DNA），这是体外，原位和体内的现代应用的关键，他们将开发混合材料模型和算法的分析和复杂和试管合奏的设计。第三，他们将推广NUPACK云Web应用程序，以包含这些新功能，使研究人员和学生能够在可扩展的NUPACK混合云中有效地利用这些独特的工具进行并行执行。 这些新的分析和设计能力预计将产生广泛的科学影响，该奖项反映了NSF的法定使命，并通过利用基金会的智力价值和更广泛的影响进行评估，被认为值得支持审查标准。

With support from the Chemical Theory, Models and Computational Methods program in the Division of Chemistry, Professor Niles A. Pierce of the California Institute of Technology (Caltech) will develop new algorithms for nucleic acid analysis and design. Nucleic acids (DNA and RNA) orchestrate life by interacting within complex biological circuits to grow, regulate, and repair organisms. Over the coming decades, engineering of DNA and RNA within the emerging fields of molecular programming, nucleic acid nanotechnology, and synthetic biology are poised to generate transformative programmable molecular and cellular technologies addressing diverse challenges to science and society ranging from environmental monitoring and biosphere engineering to diagnosis and treatment, and from renewable energy to sustainable manufacturing. To support these engineering efforts, the Pierce Lab at Caltech is engaged in a multi-decade effort to develop NUPACK (Nucleic Acid Package), a growing software suite for analyzing and designing nucleic acid structures, devices, and systems. Here, they will expand NUPACK’s capabilities by pursuing three major goals. First, they aim to develop algorithms to enable simulation of functional nucleic acid systems with moving parts. Second, they will develop analysis and design algorithms that enable treatment of systems that contain mixed materials (e.g., both DNA and RNA, or both DNA and a synthetic nucleic acid analog such as LNA) that are critical to modern applications whether in living organisms, on the laboratory bench, or in the field. Third, they will endeavor to generalize the NUPACK cloud web app to enable users to efficiently leverage these unique computational tools for both research and education. NUPACK is a growing software suite for the analysis and design of nucleic acid structures, devices, and systems serving the needs of researchers in the emerging disciplines of molecular programming, nucleic acid nanotechnology, synthetic biology, and across the life sciences. NUPACK algorithms are unique in treating complex and test tube ensembles containing arbitrary numbers of interacting strand species, providing crucial tools for capturing concentration effects essential to analyzing and designing the intermolecular interactions that are a hallmark of these fields. Here, the Pierce Lab at Caltech proposes to significantly expand NUPACK's capabilities by pursuing three major goals. First, to enable simulation of functional nucleic acid systems with moving parts, they will develop automated kinetic coarse-graining algorithms to enable kinetic analysis of complex and test tube ensembles. Second, to enable engineering of mixed-material systems (e.g., DNA/RNA or LNA/DNA) that are critical for modern applications in vitro, in situ, and in vivo, they will develop mixed-material models and algorithms for the analysis and design of complex and test tube ensembles. Third, they will generalize the NUPACK cloud web app to encompass these new capabilities, enabling researchers and students to efficiently leverage these unique tools with parallel execution in the scalable NUPACK hybrid cloud. These new analysis and design capabilities are expected to have broad scientific impact, contributing to the development of new molecular and cellular technologies that will ultimately have applications ranging from environmental monitoring and biosphere engineering to the development of nucleic acid therapeutics.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.