The Defense Advanced Research Projects Agency (DARPA) has launched a new initiative to advance the understanding of protein molecular function based on sequence and structural data. With over 300 million protein sequences and structures cataloged, but only 1% functionally characterized, DARPA’s Network of Optimal Dynamic Energy Signatures (NODES) program seeks to transform our ability to predict and control biological systems. Through this program, DARPA intends to enable early biodefense preparedness, response to biological threats, and support safer biotech innovation.
At its core, NODES is the first biophysics-guided deep learning framework designed to input protein sequences and predict their associated functions based on protein folding, protein binding, and allosteric interactions. NODES will deliver function predictions across the known protein universe. This will culminate in a universal design platform for synthetic biology, disease pathway mapping, and biosecurity applications. NODES will also estimate the evolutionary probability of protein sequences to determine whether a molecule has arisen naturally or has been synthetically engineered, possibly for use as a biothreat.
NODES is a 39-month program with a 12-month Phase 1 Base Period, a 15-month Phase 2 Option Period, and 12-month Government-only Phase 3 Option Period. Each NODES performer is expected to address all three functional areas (FAs):
- FA1: Sequence to Function through Folding
- FA2: Sequence to Function through Binding
- FA3: Sequence to Function through Allostery.
Key Dates for Proposers Day Participation
DARPA strongly encourages participation in the NODES Proposers Day to gain valuable insight into the program’s goals and submission requirements. Registration is mandatory for both in-person and webinar attendance.
- In-person Attendance (All): Friday, July 25, 2025, at 5:00 PM ET
- Webinar Attendance (Non-U.S. Citizens): Friday, July 25, 2025, at 5:00 PM ET
- Webinar Attendance (U.S. Citizens): Wednesday, July 30, 2025, at 5:00 PM ET
Why This Matters
By combining biology, biochemistry, physics, and AI to read the dynamic language of proteins, NODES represents a turning point in both fundamental biology and biodefense. The tools developed will enable the U.S. to assess unknown or engineered proteins rapidly, accelerate therapeutic discovery, and bolster national readiness against natural and synthetic biothreats.
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