ABSTRACT

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.

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