Eligible Applicants: Others (see text field entitled "Additional Information on Eligibility" for clarification)

Additional Information on Eligibility: *Who May Submit Proposals: Proposals may only be submitted by the following: -Foreign organizations: For cooperative projects involving U.S. and foreign organizations, support will only be provided for the U.S. portion. -For-profit organizations: U.S.-based commercial organizations, including small businesses, with strong capabilities in scientific or engineering research or education and a passion for innovation. -Non-profit, non-academic organizations: Independent museums, observatories, research laboratories, professional societies and similar organizations located in the U.S. that are directly associated with educational or research activities. -Other Federal Agencies and Federally Funded Research and Development Centers (FFRDCs): Contact the appropriate program before preparing a proposal for submission. -Institutions of Higher Education (IHEs) - Two- and four-year IHEs (including community colleges) accredited in, and having a campus located in the US, acting on behalf of their faculty members.Special Instructions for International Branch Campuses of US IHEs: If the proposal includes funding to be provided to an international branch campus of a US institution of higher education (including through use of subawards and consultant arrangements), the proposer must explain the benefit(s) to the project of performance at the international branch campus, and justify why the project activities cannot be performed at the US campus. -Tribal Nations: An American Indian or Alaska Native tribe, band, nation, pueblo, village, or community that the Secretary of the Interior acknowledges as a federally recognized tribe pursuant to the Federally Recognized Indian Tribe List Act of 1994, 25 U.S.C. §§ 5130-5131. *Who May Serve as PI: There are no restrictions or limits.

Agency Name: National Science Foundation

Description: The U.S. National Science Foundation’s Directorate for Technology, Innovation and Partnerships (TIP) is charged with accelerating use-inspiredand translationalresearch and development (R&D) to advance U.S. competitiveness in key technology focus areas. The Use-Inspired Acceleration of Protein Design (USPRD) initiative will accelerate the translation of novel approaches to protein design and enable new applications of importance to the U.S. bioeconomy. Significant advances have been made in the ability of researchers to predict the three-dimensional (3D) structure of proteins from primary sequence, and to use that information to design proteins with desired characteristics. These advances have been enabled by: macromolecular modeling; training data available in repositories such as the Protein Data Bank (PDB); the application of artificial intelligence (AI) and machine learning; and high-throughput protein characterization. The improved accuracy of in-silico design has reduced the number of constructs that need to be validated in costly and time-consuming “wet lab” experiments. USPRD aims to advance protein design and its applications to the next level by:

A. Accelerating the use of protein design technologies to enable applications beyond human therapeutics, e.g., applications to advanced materials, biomanufacturing, agriculture and food security, environmental remediation, sustainability, and climate-related challenges.

B. Extending the range of accurate prediction models to enable the design of enzymes and families of enzymes. This will require models and tools that account for the dynamic nature of protein structures. USPRD seeks significant breakthroughs in the application of protein design through:

a) Use-driven activities that design novel proteins with specific characteristics and demonstrate their application, e.g., the design and characterization of specific enzymes or enzyme families that promote sustainability by degrading specific bio-contaminants.

b) Infrastructure components, such as software tools, datasets, and characterization services that can readily be accessed by protein designers.

c) Designer-facing components that will ensure the accessibility of the infrastructure components and collaboration with protein designers engaged in the third-party use-driven activities.

d) Ecosystem components, such as standards and roadmaps, that help coordinate the actions of multiple parties within the emerging ecosystem. This may also include open-source software and/or data repositories.

e) Workforce components focused on the training of translational talent with the skills and passion to engage in use-driven protein design activities. USPRD will use the Ideas Lab process (see PAPPG Chapter II.F.6),starting with an intensive meeting that brings together multiple diverse perspectives. A key aim of this Ideas Lab workshop will be to identify an aggressive (but attainable) set of use-driven activities together with the infrastructure component breakthroughs, designer-facing components, and ecosystem components required to realize them. USPRD includes two tracks:

Track I. Use-driven application for small binders.

Track II. The design and use of enzymes and families of enzymes.

Grantor Contact Information: NSF grants.gov support grantsgovsupport@nsf.gov