> ## 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.

# ProteinMPNN Inverse Folding

> ProteinMPNN structure-conditioned protein sequence design

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<Note>
  **License:** ProteinMPNN is open source and free for academic and commercial use under an MIT license. Please refer to [the license](https://github.com/dauparas/ProteinMPNN/blob/main/LICENSE) for full terms.
</Note>

<p class="entity-disclaimer">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.</p>

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    ```bibtex theme={null}
    @article{dauparas2022proteinmpnn,
      title={Robust deep learning--based protein sequence design using ProteinMPNN},
      author={Dauparas, Justas and Anishchenko, Ivan and Bennett, Nathaniel and Bai, Hua and Ragotte, Robert J and Milles, Lukas F and Wicky, Basile IM and Courber, Alexis and de Haas, Rob J and Bethel, Neville and others},
      journal={Science},
      volume={378},
      number={6615},
      pages={49--56},
      year={2022},
      publisher={American Association for the Advancement of Science},
      doi={10.1126/science.add2187}
    }
    ```
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<div class="entity-contributors"><span class="entity-contributors-label">Generator contributors</span><span class="entity-contributors-people"><a class="entity-contributor" href="https://github.com/dguo8412" target="_blank" rel="noopener" title="dguo8412: 3 commits"><img noZoom class="entity-contributor-avatar" src="https://avatars.githubusercontent.com/u/46211285?v=4&s=64" alt="" loading="lazy" /><span class="entity-contributor-login">dguo8412</span></a><a class="entity-contributor" href="https://github.com/bviggiano" target="_blank" rel="noopener" title="bviggiano: 1 commit"><img noZoom class="entity-contributor-avatar" src="https://avatars.githubusercontent.com/u/21143637?v=4&s=64" alt="" loading="lazy" /><span class="entity-contributor-login">bviggiano</span></a></span></div>
Protein sequence generator using ProteinMPNN inverse folding model.

This generator uses ProteinMPNN to design protein sequences that are predicted
to fold into a given 3D backbone structure. Unlike mutation-based generators
that refine existing sequences, ProteinMPNN generates sequences directly from
structural information.

ProteinMPNN is particularly effective for:

* Redesigning existing proteins while maintaining fold
* Designing sequences for computationally generated backbones
* Creating sequence diversity for experimental screening
* Stabilizing protein structures through sequence optimization

## API Reference

<div class="api-model-section api-model-static api-config-section">
  <div class="api-model-header"><span class="api-model-badge api-config-badge">Config</span><span class="api-model-name">ProteinMPNNGeneratorConfig</span><a href="https://github.com/evo-design/proto-language/blob/d3b7822f74ea64747cc751a3b2ab1aa6b799ac47/proto_language/generator/proteinmpnn_generator.py#L20" target="_blank" class="func-table-btn func-source-btn api-model-source"><svg width="12" height="12" viewBox="0 0 24 24" fill="none" stroke="currentColor" stroke-width="2" stroke-linecap="round" stroke-linejoin="round"><polyline points="16 18 22 12 16 6" /><polyline points="8 6 2 12 8 18" /></svg> Source</a></div>

  Configuration object for ProteinMPNNGenerator.

  This class defines configuration parameters for the ProteinMPNN generator, which
  uses the ProteinMPNN inverse folding model to design protein sequences conditioned
  on a given 3D backbone structure.

  ProteinMPNN is a message-passing neural network that predicts amino acid sequences
  likely to fold into a specified protein backbone structure. It excels at redesigning
  existing proteins while maintaining structural compatibility.

  <ParamField path="model_choice" type="enum" default="proteinmpnn">
    ProteinMPNN weights: 'proteinmpnn' (general), 'abmpnn' (antibody), or 'soluble' (soluble proteins).

    Options: `proteinmpnn`, `abmpnn`, `soluble`
  </ParamField>

  <ParamField path="structure_inputs" type="array">
    Structure(s) with optional chains\_to\_redesign and fixed\_positions constraints.
  </ParamField>

  <ParamField path="output_chain_id" type="string">
    When sampling a multi-chain structure, write only this chain's sequence to the target segment.
  </ParamField>

  <ParamField path="temperature" type="number" default="0.1">
    Randomness of sampling (0-1). Near 0 is deterministic; near 1 is proportional to model probs.
  </ParamField>

  <ParamField path="excluded_amino_acids" type="array">
    Single-letter amino-acid codes to forbid in the designed sequence (e.g. 'C' to avoid disulfides).
  </ParamField>

  <ParamField path="batch_size" type="integer" default="1">
    Number of sequences to process simultaneously on GPU
  </ParamField>

  <ParamField path="device" type="string" default="cuda">
    GPU device for inference (e.g. 'cuda' or 'cuda:0').
  </ParamField>

  <ParamField path="verbose" type="boolean" default="False">
    Whether to print status messages during execution.
  </ParamField>
</div>

## Usage

```python python icon="python" theme={null}
>>> from proto_language.generator import ProteinMPNNGenerator, ProteinMPNNGeneratorConfig
>>> from proto_language.core import Segment
>>> config = ProteinMPNNGeneratorConfig(
...     structure_inputs="/path/to/backbone.pdb",
...     temperature=0.1,
... )
>>> gen = ProteinMPNNGenerator(config)
>>> segment = Segment(length=100, sequence_type="protein")
>>> gen.assign(segment)
>>> gen.sample()  # Generates num_proposals sequences from the backbone
```

## Metadata

| Property                 | Value                  |
| ------------------------ | ---------------------- |
| Key                      | `proteinmpnn`          |
| Class                    | `ProteinMPNNGenerator` |
| Category                 | `inverse_folding`      |
| Input Type               | `structure`            |
| Uses GPU                 | `True`                 |
| Supported Sequence Types | `protein`              |
| Allows Empty Start       | `False`                |
