# Simulating 500 million years of evolution with a language model

“Simulating 500 million years of evolution with a language model” (2025), by Thomas Hayes et al. Genetics and Biochemistry research paper. Original abstract below, unchanged. No free PDF was found.

- Authors: Thomas Hayes, Roshan Rao, Halil Akin, Nicholas Sofroniew, Deniz Oktay, Zeming Lin, Robert Verkuil, Vincent Q. Tran, Jonathan Deaton, Marius Wiggert et al.
- Published: January 16, 2025
- Field: Genetics and Biochemistry
- DOI: https://doi.org/10.1126/science.ads0018
- Source: https://doi.org/10.1101/2024.07.01.600583

## Abstract

More than 3 billion years of evolution have produced an image of biology encoded into the space of natural proteins. Here, we show that language models trained at scale on evolutionary data can generate functional proteins that are far away from known proteins. We present ESM3, a frontier multimodal generative language model that reasons over the sequence, structure, and function of proteins. ESM3 can follow complex prompts combining its modalities and is highly responsive to alignment to improve its fidelity. We have prompted ESM3 to generate fluorescent proteins. Among the generations that we synthesized, we found a bright fluorescent protein at a far distance (58% sequence identity) from known fluorescent proteins, which we estimate is equivalent to simulating 500 million years of evolution.

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