High-throughput Unmasking of Biological Interactomes with Binding Landscape Emulators (HUBBLE)

The Defense Advanced Research Projects Agency (DARPA) seeks proposals to develop an in-silico capability for comprehensively mapping protein-protein interactions, with validated application to identifying diagnostic and therapeutic targets for traumatic brain injury, with abstracts due November 5, 2026 at 3:00 PM ET. This is a two-stage acquisition employing Other Transactions for Research agreements; only Phase 1 awards will be made in response to this announcement, with Phase 1 spanning 12 months and Phase 2 (18 months) to be awarded separately.

Phase 1 must deliver approximately 100,000 protein-protein interactions modeled across more than 10 cellular contexts, cell types, and time points, with interactor prediction accuracy exceeding 90% and proof-of-concept predictions for protein complexes with greater than 5 interactors. Phase 2 aims to scale to 10 million interactions across 50+ unique cellular contexts. Performers must develop methods reducing computational complexity by at least seven orders of magnitude and employ both simulation and experimental approaches to capture binding energy, residence time, contact residue identity, and contextual perturbations relevant to TBI pathology, including strategies for stable dimers, transient interactions, multiprotein complexes, and biocondensate formation.

Phase 1 cost must not exceed $2.0 million for 12 months. Awards will include fixed payable milestones with payments made within 30 days of accepted invoices upon Authorized Official Representative verification of milestone completion; no advance payments are permitted. Performers receive Unlimited Rights for Government data; DARPA retains Government Purpose Rights for developed technology. Performers must achieve CMMC Level 1 certification, maintain a Unique Entity Identifier, register in SAM, and comply with foreign national participation requirements via DARPA eForm 60. NAICS 541714; PSC AC12. Technical point of contact: Dr. Abhishek Singharoy (DARPA/BTO). Administrative inquiries: Hubble@darpa.mil.