ESM3 generates esmGFP, a new fluorescent protein estimated at '500 million years of evolution' from nature
EvolutionaryScale's ESM3, a multimodal protein language model, generated esmGFP, a bright fluorescent protein only 58% identical to the closest known fluorescent protein. The authors estimate that distance equals over 500 million years of natural evolution. Published in Science (Jan 2025).
Key facts
- Announced 25 Jun 2024; Science paper published online Jan 2025
- esmGFP: 58% sequence identity to the nearest known fluorescent protein
- '500 million years of evolution' is the authors' estimate
Science result
- Field
- biology / protein design
- Problem
- Generating functional proteins far from natural sequences
- Result
- A functional fluorescent protein with low identity to any natural protein, generated by a language model.
- AI system
- ESM3
- Human role
- Human-designed prompting and lab validation
- Verification
- Peer-reviewed in Science; lab-validated fluorescence
- Status
- confirmed
What happened
ESM3 was prompted with a few key residues of GFP's chromophore site and generated whole new proteins. One, esmGFP, glowed after refinement rounds.
Why it matters
It showed language models producing functional proteins far outside the natural sequence space.
Changelog
- 2026-09-29: created
Related events
Sources (2)
- paperSimulating 500 million years of evolution with a language model (Science)
- officialEvolutionaryScale: ESM3 release
id: 2024-06-25-esm3-esmgfp · updated 2026-09-29 · open in the interactive timeline