> ## Documentation Index > Fetch the complete documentation index at: https://proto.evodesign.org/docs/llms.txt > Use this file to discover all available pages before exploring further. # ESM3 Protein Language Model > ESM-3 open masked protein language model for local sequence mutation/refinement
ESM3 Protein Language Model
**License:** ESM3 is open source and free for academic and commercial use under an MIT license. Please refer to [the license](https://github.com/Biohub/esm/blob/main/LICENSE.md) for full terms.

This generator is open source. Any third-party models, product names, or trademarks referenced are the property of their respective owners, and Proto is not affiliated with them.

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evo-design/proto-language/proto\_language/generator/esm3\_generator.py
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```bibtex theme={null} @article{hayes2025esm3, title={Simulating 500 million years of evolution with a language model}, author={Hayes, Thomas and Rao, Roshan and Akin, Halil and Sofroniew, Nicholas J. and Oktay, Deniz and Lin, Zeming and Verkuil, Robert and Tran, Vincent Q. and Deaton, Jonathan and Wiggert, Marius and Badkundri, Rohil and Shafkat, Irhum and Gong, Jun and Derry, Alexander and Molina, Raul S. and Thomas, Neil and Khan, Yousuf A. and Mishra, Chetan and Kim, Carolyn and Bartie, Liam J. and Nemeth, Matthew and Hsu, Patrick D. and Sercu, Tom and Candido, Salvatore and Rives, Alexander}, journal={Science}, volume={387}, number={6736}, pages={850--858}, year={2025}, publisher={American Association for the Advancement of Science}, doi={10.1126/science.ads0018} } @software{evolutionaryscale_2024, author={{EvolutionaryScale Team}}, title={evolutionaryscale/esm}, year={2024}, publisher={Zenodo}, doi={10.5281/zenodo.14219303}, url={https://doi.org/10.5281/zenodo.14219303} } ```
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Protein sequence mutation/refinement generator using ESM3 open language model. This generator uses the open-source ESM3 protein language model to refine existing protein sequences through iterative mutation. It masks positions according to the configured masking strategy and samples biologically plausible amino acids at those positions. The generator category is `"mutation"`, indicating it refines proposal sequences through targeted mutations. ## API Reference
ConfigESM3GeneratorConfig Source
Configuration object for ESM3Generator. This class defines configuration parameters for the ESM3 generator, which uses the open-source ESM3 protein language model to refine existing protein sequences through iterative mutation of masked positions. In Proto Language, ESM3 is registered as a mutation-category generator that edits the supplied starting sequence; the segment must carry a sequence (directly or from a prior optimizer stage). ESM3 is the open-source version of EvolutionaryScale's protein language model. ESM-3 model variant to load. Controls which positions to mask for sampling. Default: random 30%. 'single\_pass' fills all masks in one forward; 'iterative\_refinement' uses ESM-3 batch generation. Options: `single_pass`, `iterative_refinement` Scales the randomness of sampling by adjusting probability distribution sharpness. Nucleus sampling threshold; 1.0 disables Iterative-refinement decoding steps; diminishing returns above 20 Unmask schedule across rounds; 'cosine' fronts more commits late Options: `cosine`, `linear` Position-selection per round; 'entropy' commits the most-confident first Options: `random`, `entropy` Anneal temperature toward 0 across rounds GPU device to run ESM3 on (e.g. 'cuda' or 'cuda:0'). Number of sequences to process simultaneously on GPU
## Usage ```python python icon="python" theme={null} >>> from proto_language.generator import ESM3Generator, ESM3GeneratorConfig >>> from proto_language.core import Segment >>> from proto_tools.transforms.masking import MaskingStrategy >>> config = ESM3GeneratorConfig( ... temperature=1.0, ... masking_strategy=MaskingStrategy(num_mutations=5), ... ) >>> gen = ESM3Generator(config) >>> segment = Segment(sequence="M" * 100, sequence_type="protein") >>> gen.assign(segment) >>> gen.sample() # Re-samples 5 randomly masked positions ``` ## Metadata | Property | Value | | ------------------------ | ------------------- | | Key | `esm3` | | Class | `ESM3Generator` | | Category | `mutation` | | Input Type | `starting_sequence` | | Uses GPU | `True` | | Supported Sequence Types | `protein` | | Allows Empty Start | `False` |