> ## 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.

# Protein Complexity

> Evaluate protein sequence complexity using segmasker to detect low-complexity regions

<div class="page-hero">
  <img class="page-hero-banner" src="https://proto-bio.github.io/proto-assets/images/constraint/protein-complexity/hero.png" alt="Protein Complexity" />
</div>

<Note>
  **License:** Segmasker is licensed under Custom (NCBI BLAST+ public domain). Please refer to [the license](https://www.ncbi.nlm.nih.gov/IEB/ToolBox/CPP_DOC/lxr/source/scripts/projects/blast/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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<a href="https://github.com/evo-design/proto-language/blob/d3b7822f74ea64747cc751a3b2ab1aa6b799ac47/proto_language/constraint/protein_quality/protein_complexity_constraint.py#L51" target="_blank" class="tab-panel source-panel" data-tab="source-constraint-protein-complexity">
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    <span class="source-path">evo-design/proto-language<span class="source-subpath">/proto\_language/constraint/protein\_quality/protein\_complexity\_constraint.py</span></span>
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  <span class="panel-goto-btn source-goto-btn"><span><svg width="14" height="14" viewBox="0 0 24 24" fill="currentColor"><path d="M12 0C5.37 0 0 5.37 0 12c0 5.31 3.435 9.795 8.205 11.385.6.105.825-.255.825-.57 0-.285-.015-1.23-.015-2.235-3.015.555-3.795-.735-4.035-1.41-.135-.345-.72-1.41-1.23-1.695-.42-.225-1.02-.78-.015-.795.945-.015 1.62.87 1.845 1.23 1.08 1.815 2.805 1.305 3.495.99.105-.78.42-1.305.765-1.605-2.67-.3-5.46-1.335-5.46-5.925 0-1.305.465-2.385 1.23-3.225-.12-.3-.54-1.53.12-3.18 0 0 1.005-.315 3.3 1.23.96-.27 1.98-.405 3-.405s2.04.135 3 .405c2.295-1.56 3.3-1.23 3.3-1.23.66 1.65.24 2.88.12 3.18.765.84 1.23 1.905 1.23 3.225 0 4.605-2.805 5.625-5.475 5.925.435.375.81 1.095.81 2.22 0 1.605-.015 2.895-.015 3.3 0 .315.225.69.825.57A12.02 12.02 0 0024 12c0-6.63-5.37-12-12-12z" /></svg> View source</span></span>
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<div class="tab-panel cite-panel" data-tab="cite-constraint-protein-complexity">
  <div class="cite-code-wrap">
    ```bibtex theme={null}
    @article{wootton1993seg,
      title={Statistics of local complexity in amino acid sequences and sequence databases},
      author={Wootton, John C and Federhen, Scott},
      journal={Computers \& Chemistry},
      volume={17},
      number={2},
      pages={149--163},
      year={1993},
      publisher={Elsevier},
      doi={10.1016/0097-8485(93)85006-x}
    }

    @article{camacho2009blastplus,
      title={BLAST+: architecture and applications},
      author={Camacho, Christiam and Coulouris, George and Avagyan, Vahram and Ma, Ning and Papadopoulos, Jason and Bealer, Kevin and Madden, Thomas L},
      journal={BMC Bioinformatics},
      volume={10},
      pages={421},
      year={2009},
      publisher={BioMed Central},
      doi={10.1186/1471-2105-10-421}
    }
    ```
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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: 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></span></div>
Evaluate protein sequence complexity using segmasker to detect low-complexity regions.

This constraint function uses NCBI's segmasker tool to identify low-complexity
regions in protein sequences. Low-complexity regions contain repetitive or
compositionally biased amino acid sequences that may indicate poor protein
quality, tandem repeats, or non-functional segments. The constraint penalizes
sequences where the fraction of low-complexity regions exceeds a specified
threshold.

The function processes multiple sequences simultaneously. Segmasker marks
low-complexity regions by replacing them with lowercase characters, and
the constraint calculates the fraction of masked positions.

## 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">ProteinComplexityConfig</span><a href="https://github.com/evo-design/proto-language/blob/d3b7822f74ea64747cc751a3b2ab1aa6b799ac47/proto_language/constraint/protein_quality/protein_complexity_constraint.py#L15" 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 protein complexity constraint.

  This class defines configuration parameters for evaluating protein sequence
  complexity using NCBI's segmasker tool. The constraint detects and penalizes
  low-complexity regions, which contain repetitive or biased amino acid
  compositions that may indicate poor protein quality or non-functional sequences.

  <ParamField path="max_low_complexity" type="number" default="0.2">
    Maximum acceptable fraction of low-complexity regions (repetitive/biased amino acid compositions)
  </ParamField>
</div>

<div class="api-model-section api-model-static api-output-section">
  <div class="api-model-header"><span class="api-model-badge api-output-badge">Returns</span><span class="api-model-name">ConstraintOutput</span></div>

  One result per sequence. A score of 0.0 indicates
  acceptable complexity (low-complexity fraction at or below threshold)
  and higher values indicate excessive low-complexity content. Scores
  scale linearly with excess low-complexity beyond the threshold, capped
  at 1.0. `metadata` carries:

  * `low_complexity_fraction`: Float fraction of sequence identified as
    low-complexity (0.0-1.0)
  * `low_complexity_count`: Integer count of positions masked as
    low-complexity (from segmasker)
</div>

## Usage

Evaluating protein complexity:

```python python icon="python" theme={null}
>>> from proto_language.core import Sequence, SequenceType
>>> config = ProteinComplexityConfig(max_low_complexity=0.2)
>>> seq = Sequence("MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSF", "protein")
>>> results = protein_complexity_constraint([(seq,)], config)
>>> print(results[0].score)  # 0.0 if low-complexity <= 20%
>>> print(results[0].metadata["low_complexity_fraction"])  # e.g., 0.15
>>> print(results[0].metadata["low_complexity_count"])  # e.g., 5
```

## Metadata

| Property        | Value                           |
| --------------- | ------------------------------- |
| Key             | `protein-complexity`            |
| Function        | `protein_complexity_constraint` |
| Category        | `protein_quality`               |
| Mode            | `discrete`                      |
| Uses GPU        | `False`                         |
| Supported Types | `protein`                       |
