> ## 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.

# MPNN Perplexity

> Score protein sequences by ProteinMPNN perplexity against a fixed backbone; differentiable.

<div class="page-hero">
  <img class="page-hero-banner" src="https://proto-bio.github.io/proto-assets/images/constraint/mpnn-perplexity/hero.png" alt="MPNN Perplexity" />
</div>

<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 constraint 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>

<hr class="entity-rule" />

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  <div class="cite-code-wrap">
    ```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}
    }
    ```
  </div>

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<div class="entity-contributors"><span class="entity-contributors-label">Constraint contributors</span><span class="entity-contributors-people"><a class="entity-contributor" href="https://github.com/dguo8412" target="_blank" rel="noopener" title="dguo8412: 2 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></span></div>
Score proposals by ProteinMPNN perplexity against the configured backbone.

## 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">MpnnPerplexityConfig</span><a href="https://github.com/evo-design/proto-language/blob/d3b7822f74ea64747cc751a3b2ab1aa6b799ac47/proto_language/constraint/sequence_scoring/mpnn_perplexity_constraint.py#L32" 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 for ProteinMPNN perplexity scoring.

  <ParamField path="structure_input" type="InverseFoldingStructureInput" required>
    Backbone structure, optional chains\_to\_redesign, and fixed positions for direct ProteinMPNN scoring.
  </ParamField>

  <ParamField path="model_choice" type="enum" default="proteinmpnn">
    Weights: proteinmpnn (=v\_48\_020), v\_48\_\{002,010,030} noise variants, abmpnn, soluble.

    Options: `proteinmpnn`, `v_48_002`, `v_48_010`, `v_48_030`, `abmpnn`, `soluble`
  </ParamField>

  <ParamField path="temperature" type="number" default="1.0">
    Softmax temperature for relaxing optimizer logits before ProteinMPNN scoring.
  </ParamField>

  <ParamField path="use_ste" type="boolean" default="True">
    Hard one-hot forward pass with soft-probability gradients.
  </ParamField>

  <ParamField path="device" type="string" default="cuda">
    Device for ProteinMPNN execution, e.g. 'cuda' or 'cuda:0'.
  </ParamField>

  <ParamField path="seed" type="integer">
    Seed for ProteinMPNN decoding-order sampling. None lets proto-tools choose a fresh seed.
  </ParamField>

  <ParamField path="score_mode" type="enum" default="ppl">
    Return ProteinMPNN perplexity by default, or raw mean NLL when set to 'nll'.

    Options: `nll`, `ppl`
  </ParamField>

  <ParamField path="logit_scale" type="number" default="1.0">
    Pre-scale raw logits before ProteinMPNN; gradients are scaled back by the same factor.
  </ParamField>

  <ParamField path="sequence_bias" type="SequenceLogitBiasConfig">
    Declarative sequence-symbol bias (canonical 20-AA protein) added before ProteinMPNN.
  </ParamField>
</div>

## Usage

```python python icon="python" theme={null}
from proto_language.core import Constraint
from proto_language.constraint import mpnn_perplexity_constraint, MpnnPerplexityConfig

constraint = Constraint(
    inputs=[segment],
    function=mpnn_perplexity_constraint,
    function_config=MpnnPerplexityConfig(
        # Configure parameters here
    ),
)

scores = constraint.evaluate()
```

## Metadata

| Property        | Value                        |
| --------------- | ---------------------------- |
| Key             | `mpnn-perplexity`            |
| Function        | `mpnn_perplexity_constraint` |
| Category        | `sequence_scoring`           |
| Mode            | `dual`                       |
| Uses GPU        | `True`                       |
| Supported Types | `protein`                    |
