# Structure-Guided Adaptive Propagation for Protein-Protein Interaction Site Prediction

arXiv: https://arxiv.org/abs/2606.01781 · HTML: https://mlsanity.com/paper/2606.01781/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 6 of its 44 references that are in the map.
- First posted on arXiv 1 Jun 2026.

## Builds on (most cited first, 6 of 6)

- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Deeper Insights into Graph Convolutional Networks for Semi-Supervised Learning](https://mlsanity.com/paper/1801.07606/) (2018)
- [Predict then Propagate: Graph Neural Networks meet Personalized PageRank](https://mlsanity.com/paper/1810.05997/) (2018)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [Pay Less Attention with Lightweight and Dynamic Convolutions](https://mlsanity.com/paper/1901.10430/) (2019)
- [MUSE: Parallel Multi-Scale Attention for Sequence to Sequence Learning](https://mlsanity.com/paper/1911.09483/) (2019)

## Abstract (arXiv)

Accurate prediction of protein-protein interaction sites (PPIS) is essential for understanding cellular processes, disease mechanisms, and therapeutic target discovery. Graph-based deep learning has advanced PPIS prediction by incorporating residue-level structural context. However, most graph-based models still rely on fixed propagation schemes that treat all residues similarly, despite the structural and functional heterogeneity of protein interfaces. Such propagation may limit the ability to adapt information diffusion to local geometric environments, making it difficult to distinguish true interaction sites from structurally similar non-interacting neighbors. We present SGAP-PPIS, a structure-guided adaptive propagation model for PPIS prediction. Rather than using a fixed propagation mechanism, SGAP-PPIS leverages multi-scale geometric states from an equivariant graph neural network to generate residue-wise propagation coefficients. This design allows each residue to adaptively balance local feature preservation and neighborhood diffusion according to its geometric microenvironment. Experimental results show that SGAP-PPIS achieves competitive performance among the state-of-the-art methods on Test60. Ablation studies show that geometry-conditioned adaptive propagation, scale-aligned geometric guidance, and multi-step propagation-state representation jointly drive these improvements.