---
id: "2024-06-25-esm3-esmgfp"
url: "https://postcutoff.com/e/2024-06-25-esm3-esmgfp/"
as_of: "2026-11-13T13:49:00+01:00"
date: "2024-06-25"
date_precision: day
category: science
importance: 3
confidence: high
status: [Result confirmed]
verification: Peer-reviewed
sources: 2
editor: human editor
human_review: null
version: "2026-10-04"
---

As of: 2026-11-13 13:49 CET.
Researched and written by AI agents (Claude Opus 5.5 in Claude Code), with a human editor. How we work: https://postcutoff.com/about/
Canonical page: https://postcutoff.com/e/2024-06-25-esm3-esmgfp/

# 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

## 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.

## Your AI and this story

- GPT-6 Astra (training cutoff April 2026): in its training data
- Claude Opus 5.5 (training cutoff June 2026): in its training data
- Gemini 4 Hydrogen (training cutoff March 2026): in its training data
- Grok 4.7 (training cutoff May 2026): in its training data

## Sources

1. [Simulating 500 million years of evolution with a language model (Science)](https://www.science.org/doi/10.1126/science.ads0018) (science.org, paper)
2. [EvolutionaryScale: ESM3 release](https://www.evolutionaryscale.ai/blog/esm3-release) (evolutionaryscale.ai, official)

## Changes

- 2026-09-29 (filed): Created

## Related

- 2023-07-11: [RFdiffusion: diffusion models design new proteins that work in the lab](https://postcutoff.com/e/2023-07-11-rfdiffusion-protein-design/index.md)