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```bibtex theme={null} @article{dunbrack_2025_ipsae, title={R\={e}s ipSAE loquuntur: What's wrong with AlphaFold's ipTM score and how to fix it}, author={Dunbrack, Roland L.}, journal={bioRxiv}, year={2025}, doi={10.1101/2025.02.10.637595}, url={https://www.biorxiv.org/content/10.1101/2025.02.10.637595v2}, } @article{zhu_2023_pdockq2, title={Evaluation of AlphaFold-Multimer prediction on multi-chain protein complexes}, author={Zhu, Wensi and Shenoy, Aditi and Kundrotas, Petras and Elofsson, Arne}, journal={Bioinformatics}, volume={39}, number={7}, pages={btad424}, year={2023}, doi={10.1093/bioinformatics/btad424}, } @article{bryant_2022_pdockq, title={Improved prediction of protein-protein interactions using AlphaFold2}, author={Bryant, Patrick and Pozzati, Gabriele and Elofsson, Arne}, journal={Nature Communications}, volume={13}, number={1}, pages={1265}, year={2022}, doi={10.1038/s41467-022-28865-w}, } @article{kim_2024_lis, title={Enhanced Protein-Protein Interaction Discovery via AlphaFold-Multimer}, author={Kim, Ah-Ram and Hu, Yanhui and Comjean, Aram and Rodiger, Jonathan and Mohr, Stephanie E. and Perrimon, Norbert}, journal={bioRxiv}, year={2024}, doi={10.1101/2024.02.19.580970}, url={https://www.biorxiv.org/content/10.1101/2024.02.19.580970v1}, } ```

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### IPSAE Interface Scoring (`ipsae-scoring`) Scores a cofolded protein complex by computing ipSAE, pDockQ2, LIS, pDockQ, and interface pTM for a designated binder chain against one or more target chains. The tool takes a `Structure` with per-residue pLDDT in the B-factor column and the PAE matrix attached at `structure.metrics["pae"]`, runs the IPSAE scoring program, and returns the headline scores together with a full per-chain-pair breakdown. #### API Reference

Source Cofolded complex with per-residue pLDDT in the B-factor column and the PAE matrix attached at `structure.metrics['pae']` as a square `list[list[float]]`. Raw structure content in PDB or CIF format. Format of the content string (auto-detected if omitted). What the B-factor column represents. Optional source identifier (filepath or tool name). Associated metrics (e.g., pLDDT, pTM scores, per-chain lists, pairwise matrices). None values are stripped at construction. Single-character chain ID of the binder. The selected chain ID. Target chain ID(s). Chain IDs in the selection.

Source PAE cutoff in Å for interface residue detection. CA-CA distance cutoff in Å for contact detection. Verbosity level (0=quiet, 1=info, 2=debug, 3=raw subprocess stderr). `True` is coerced to `1` and `False` to `0`. Device to run the tool on. Maximum execution time in seconds. `None` waits indefinitely. Random seed. When set, tools run reproducibly up to small GPU float noise (see `BaseToolOutput.approx_equal`), and the seed participates in cache keys. When None, cacheable seed-sensitive tools skip cache until seeded.

Source Scalar metrics plus per-chain-pair breakdown. Full per-chain-pair breakdown. Name of the metric that best summarizes the result overall (e.g. `"avg_plddt"` for AlphaFold2). Used by downstream UI and reporting to pick a headline value. Concrete Metrics subclass tag; enables typed reconstruction after a serialization round-trip. **Metrics** | Metric | Type | Range | Availability | | ------------ | ----- | ---------- | ------------ | | `ipsae` | float | 0.0 to 1.0 | always | | `pdockq2` | float | 0.0 to 1.0 | always | | `lis` | float | 0.0 to 1.0 | always | | `pdockq` | float | 0.0 to 1.0 | always | | `iptm_d0chn` | float | 0.0 to 1.0 | always |

#### Applications This tool is appropriate for ranking and filtering cofolded complexes from structure-prediction tools such as AlphaFold 3, Chai-1, Boltz, or Protenix. Representative applications include scoring candidate protein binders from a design pipeline, identifying the most promising poses in a multi-chain prediction ensemble, and any analysis that benefits from multiple complementary interface-quality scores in a single call rather than running several scoring programs in sequence. #### Usage Tips * **The PAE matrix is required and must be attached at `structure.metrics["pae"]` as a square `list[list[float]]`.** The dimension should match the total residue count of the structure. The input is rejected when the matrix is missing or not square. * **Per-residue pLDDT must be supplied via the B-factor column.** Structure predictors in proto-tools return the correct `b_factor_type` automatically, and `Structure.from_file()` auto-detects it for AlphaFold DB and ModelArchive files. For manually provided structures from other sources, pass `b_factor_type=BFactorType.PLDDT` (raw 0 to 100) or `BFactorType.NORMALIZED_PLDDT` (0 to 1) explicitly. The input is rejected when `b_factor_type` is any other value, since pDockQ and pDockQ2 would otherwise be computed incorrectly. * **Missing or duplicated chains are rejected.** The binder chain must not also appear in `target_chains`, and every requested chain must be present in the structure. Single-character chain identifiers are also required because IPSAE reads PDB-format input. Multi-character mmCIF chain labels should be shortened with `Structure.to_pdb_with_chain_mapping()` before scoring. * **The tool implementation does not check that the PAE matrix is aligned with the structure residue by residue.** It only confirms the matrix is square and two-dimensional. The caller is responsible for ensuring the PAE rows and columns match the residue order in the structure. A misaligned PAE matrix produces silently meaningless scores rather than an error. * **The top-level scores report the symmetric maximum value for the binder-target interface.** The full directional and symmetric breakdown for every chain pair is available on `result.metrics.chain_pair_results`. When no symmetric pair matches the binder-target combination, the tool raises a `ValueError` listing the available chain pairs so the chain labels can be corrected. * **`pae_cutoff` and `distance_cutoff` control the interface definition.** Both default to `10.0` Å. Lower values define a tighter interface and reduce the number of residues contributing to each score. Use a tighter cutoff when comparing interfaces of similar overall size or when assessing buried interfaces. * **An empty interface returns zeros for every score.** When no residues fall within both cutoffs across the binder-target chain pair, every metric is `0.0`. Verify the chain identifiers and cutoff values before interpreting an all-zero result as a poor interface.