# ESM3 (EvolutionaryScale)

Source: https://onco.cc/technologies/esm3/  
OnCo record `esm3` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

ESM3 is a generative protein model that designed a working fluorescent protein far from any natural sequence.

## Summary

ESM3 from EvolutionaryScale is a generative protein language model that jointly represents sequence, structure and function as tokens in a masked multimodal transformer, so a user can prompt it with any combination of these and ask it to fill in the rest. The Science 2025 paper describes models up to 98B parameters and the design of esmGFP, a working fluorescent protein far from any natural sequence, demonstrating generation of novel functional proteins. It is aimed at protein engineers and drug designers exploring binders, enzymes and antibodies, including for cancer targets. The largest weights are closed, with smaller versions open, so the strongest capabilities are available only through the company. For a newcomer: ESM3 has learned enough about proteins to invent new ones that work.

## Fields

- Kind: Technology
- Status: emerging
- Last checked: 2026-09-08
- Tags: foundation-model; protein-design
- Principle: ESM3 is a masked multimodal transformer over protein tokens.
- Since: 2024
- Strengths: Joint sequence-structure-function
- Limitations: Largest weights closed

## Sources

- Science 2025: https://doi.org/10.1126/science.ads0018

## Connected records

- fronts: [AI & Computation](https://onco.cc/fronts/ai-computation/), [Drug Discovery Platforms](https://onco.cc/fronts/drug-discovery/)
- technologies: [AI-driven drug & target discovery](https://onco.cc/technologies/ai-drug-design/)
- companies: [EvolutionaryScale](https://onco.cc/companies/evolutionaryscale/)
- key papers: [Simulating 500 million years of evolution with a language model](https://onco.cc/key-papers/paper-hayes-science/)
- roadmaps: [AI in oncology roadmap: pattern readers → foundation models → agents in the workflow](https://onco.cc/roadmaps/ai-oncology-roadmap/), [Drug discovery roadmap: screening in mice → maps of dependency → designing in silico](https://onco.cc/roadmaps/drug-discovery-roadmap/)

---
JSON: https://onco.cc/api/v1/entities/esm3.json