# PairSAE: Mechanistic Interpretability from Pair Representations in Protein Co-Folding

arXiv: https://arxiv.org/abs/2606.27440 · HTML: https://mlsanity.com/paper/2606.27440/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Interpreting biomedical and science models, one of 13 directions in Mechanistic interpretability.
- Builds on 11 of its 35 references that are in the map.
- First posted on arXiv 25 Jun 2026.

## Placed in

- Mechanistic interpretability / [Interpreting biomedical and science models](https://mlsanity.com/mechinterp/interpreting-biomedical-and-science-models/)

## Builds on (most cited first, 11 of 11)

- [Sparse Autoencoders Find Highly Interpretable Features in Language Models](https://mlsanity.com/paper/2309.08600/) (2023)
- [Toy Models of Superposition](https://mlsanity.com/paper/2209.10652/) (2022)
- [Scaling and evaluating sparse autoencoders](https://mlsanity.com/paper/2406.04093/) (2024)
- [Scaling Monosemanticity: Extracting Interpretable Features from Claude 3 Sonnet](https://mlsanity.com/paper/2605.29358/) (2026)
- [Learning Multi-Level Features with Matryoshka Sparse Autoencoders](https://mlsanity.com/paper/2503.17547/) (2025)
- [BatchTopK Sparse Autoencoders](https://mlsanity.com/paper/2412.06410/) (2024)
- [Polysemanticity and Capacity in Neural Networks](https://mlsanity.com/paper/2210.01892/) (2022)
- [InterPLM: Discovering Interpretable Features in Protein Language Models via Sparse Autoencoders](https://mlsanity.com/paper/2412.12101/) (2024)
- [Sparse Autoencoders for Hypothesis Generation](https://mlsanity.com/paper/2502.04382/) (2025)
- [Interpreting and Steering Protein Language Models through Sparse Autoencoders](https://mlsanity.com/paper/2502.09135/) (2025)
- [Towards Interpretable Protein Structure Prediction with Sparse Autoencoders](https://mlsanity.com/paper/2503.08764/) (2025)

## Abstract (arXiv)

Foundation models for structural biology have achieved remarkable performance in predicting biomolecular structure and show promise for the design of proteins and small molecules. Yet understanding which internal features drive their outputs remains challenging. Standard sparse autoencoders (SAEs), effective on transformer-style sequence embeddings, do not transfer cleanly to pairformer-like architectures: naively operating on pairwise representations yields a quadratic blow-up of features and obscures concepts distributed jointly across sequence and pair representations. We introduce PairSAE, which summarizes pairwise tensors via an N-mode SVD into token-wise interaction roles, then uses a sparse autoencoder to learn a shared set of token-level features that decode into both sequence and pair representations. Evaluated on Boltz-2 activations for PLINDER protein-ligand complexes, PairSAE yields interpretable features that align with UniProt annotations and predict Boltz-2 affinity values. These results indicate that PairSAE links the latent space of foundation models for structural biology to interpretable structural concepts, clarifying what the model "knows" while avoiding pairformer-induced pitfalls that limit conventional SAEs.