Software Elements: NUPACK: Molecular Programming in the Cloud

生命是由可编程的生物分子（DNA、RNA和蛋白质）精心策划的，它们在复杂的分子机器和生物电路中相互作用，以生长、调节和修复生物体。这些生物学原理证明激发了分子编程、核酸纳米技术和合成生物学等新领域的各种工程努力。在未来的几十年里，这些领域将产生变革性的可编程分子和细胞技术，解决科学和社会的挑战，从神经科学和发展，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，PI正在进行数十年的努力开发NUPACK（核酸包），这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。自2007年推出以来，NUPACK的使用已经发展到NUPACK计算资源经常被研究社区所淹没的地步。通过这项工作，NUPACK web应用程序将从头开始重新架构，以便在云中运行，使资源能够动态扩展，以响应研究人员的需求高峰和年复一年的增长。NUPACK用户界面将大大扩展，使用户能够利用下一代分析和设计工具。此外，重新架构的web应用程序将受益于NUPACK科学代码库的完全重写（从NUPACK 3.2移动到4.0），以实现显著的计算加速和利用增强的物理模型。有了云端的NUPACK，用户将能够在规模和科学范围方面执行远远超出当前能力的计算，从而探索可编程分子技术不断发展的前沿。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，服务于分子编程，核酸纳米技术和合成生物学等新兴学科的研究人员的需求。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，为捕获分析和设计这些新领域标志的分子间相互作用所必需的浓度效应提供了关键工具。使用率已经增加到NUPACK计算集群经常不堪重负的地步。通过提出的工作，NUPACK web应用程序将被重新架构，以实现在云上的部署，通过一次点击启动的数十到数千个作业的容器化，并使资源的规模能够每分钟和每年动态变化。为了转移到NUPACK计算硬件和工程支持的可持续模式，将创建NUPACK用户帐户，使用户能够查看和检索旧作业，无缝地支付用于其工作的云计算周期，并为NUPACK软件工程师提供与他们使用这种非营利性学术资源成比例的增量支持。用户界面将大大扩展，使用户能够利用增强的NUPACK后端的新功能，包括复杂和试管集成的动力学分析，试管集成的动力学设计，试管集成中大规模伪结结构的平衡设计，以及为定制实验条件生成的新的计算参数化物理模型的使用。重新架构的web应用程序还将受益于完全重写的NUPACK科学代码库，具有改进的实现、降低复杂性的算法、溢出安全的求值代数和扩展的物理模型。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。

Life is orchestrated by programmable biomolecules (DNA, RNA, and proteins) that interact within complex molecular machines and biological circuits to grow, regulate, and repair organisms. These biological proofs-of-principle inspire diverse engineering efforts within the new fields of molecular programming, nucleic acid nanotechnology, and synthetic biology. Over the coming decades, these fields are poised to generate transformative programmable molecular and cellular technologies addressing challenges to science and society ranging from neuroscience and development, to diagnosis and treatment, and from renewable energy to sustainable manufacturing. To support these engineering efforts, the PI 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. Launched in 2007, NUPACK usage has grown to the point where the NUPACK compute resource is frequently overwhelmed by the research community. With the proposed work, the NUPACK web application will be re-architected from the ground up to run in the cloud, enabling the resource to scale dynamically in response to spikes in researcher demand and to growth year-over-year. The NUPACK user interface will be substantially expanded to allow users to harness next-generation analysis and design tools. Additionally, the re-architected web application will benefit from a complete re-write of the NUPACK scientific code base (moving from NUPACK 3.2 to 4.0) to achieve dramatic computational speed-ups and exploit enhanced physical models. With NUPACK in the cloud, users will be able to perform calculations far beyond current capabilities both in terms of scale and scientific scope, enabling exploration of a growing frontier of programmable molecular technologies.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, and synthetic biology. 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 new fields. Usage has increased to the point where the NUPACK compute cluster is frequently overwhelmed. With the proposed work, the NUPACK web application will be re-architected to enable deployment on the cloud, containerizing the dozens to thousands of jobs that are launched by a single click, and enabling the scale of the resource to vary dynamically minute-to-minute and year-over-year. To move to a sustainable model for NUPACK compute hardware and engineering support, NUPACK user accounts will be created that enable users to view and retrieve old jobs, to seamlessly pay for the cloud compute cycles that are used for their jobs, and to provide incremental support for the NUPACK Software Engineer proportional to their usage of this non-profit academic resource. The user interface will be substantially expanded to allow users to harness the new capabilities of the enhanced NUPACK backend, including kinetic analysis for complex and test tube ensembles, kinetic design for test tube ensembles, equilibrium design for large-scale pseudo-knotted structures in test tube ensembles, and use of new computationally parameterized physical models generated for custom experimental conditions. The re-architected web application will also benefit from a complete re-write of the NUPACK scientific code base, featuring improved implementations, reduced-complexity algorithms, overflow-safe evaluation algebras, and expanded physical models.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.