# Towards Multiscale Graph-based Protein Learning with Geometric Secondary Structural Motifs

arXiv: https://arxiv.org/abs/2602.00862 · HTML: https://mlsanity.com/paper/2602.00862/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 25 of its 50 references that are in the map.
- First posted on arXiv 31 Jan 2026.

## Builds on (most cited first, 25 of 25)

- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Mamba: Linear-Time Sequence Modeling with Selective State Spaces](https://mlsanity.com/paper/2312.00752/) (2023)
- [How Powerful are Graph Neural Networks?](https://mlsanity.com/paper/1810.00826/) (2018)
- [Fast Graph Representation Learning with PyTorch Geometric](https://mlsanity.com/paper/1903.02428/) (2019)
- [Weisfeiler and Leman Go Neural: Higher-order Graph Neural Networks](https://mlsanity.com/paper/1810.02244/) (2018)
- [GemNet: Universal Directional Graph Neural Networks for Molecules](https://mlsanity.com/paper/2106.08903/) (2021)
- [Learning from Protein Structure with Geometric Vector Perceptrons](https://mlsanity.com/paper/2009.01411/) (2020)
- [Evaluating Protein Transfer Learning with TAPE](https://mlsanity.com/paper/1906.08230/) (2019)
- [An Empirical Study of Mamba-based Language Models](https://mlsanity.com/paper/2406.07887/) (2024)
- [Protein Representation Learning by Geometric Structure Pretraining](https://mlsanity.com/paper/2203.06125/) (2022)
- [On the Expressive Power of Geometric Graph Neural Networks](https://mlsanity.com/paper/2301.09308/) (2023)
- [ProtST: Multi-Modality Learning of Protein Sequences and Biomedical Texts](https://mlsanity.com/paper/2301.12040/) (2023)
- [SE(3) Equivariant Graph Neural Networks with Complete Local Frames](https://mlsanity.com/paper/2110.14811/) (2021)
- [ComENet: Towards Complete and Efficient Message Passing for 3D Molecular Graphs](https://mlsanity.com/paper/2206.08515/) (2022)
- [Learning Hierarchical Protein Representations via Complete 3D Graph Networks](https://mlsanity.com/paper/2207.12600/) (2022)
- [Equivariant Graph Neural Networks for 3D Macromolecular Structure](https://mlsanity.com/paper/2106.03843/) (2021)
- [Multi-Scale Representation Learning on Proteins](https://mlsanity.com/paper/2204.02337/) (2022)
- [A new perspective on building efficient and expressive 3D equivariant graph neural networks](https://mlsanity.com/paper/2304.04757/) (2023)
- [DeepSF: deep convolutional neural network for mapping protein sequences to folds](https://mlsanity.com/paper/1706.01010/) (2017)
- [Molformer: Motif-based Transformer on 3D Heterogeneous Molecular Graphs](https://mlsanity.com/paper/2110.01191/) (2021)
- [Llamba: Scaling Distilled Recurrent Models for Efficient Language Processing](https://mlsanity.com/paper/2502.14458/) (2025)
- [Molecular Representation Learning via Heterogeneous Motif Graph Neural Networks](https://mlsanity.com/paper/2202.00529/) (2022)
- [ProtChatGPT: Towards Understanding Proteins with Large Language Models](https://mlsanity.com/paper/2402.09649/) (2024)
- [Multi-Scale Representation Learning for Protein Fitness Prediction](https://mlsanity.com/paper/2412.01108/) (2024)
- [Clustering for Protein Representation Learning](https://mlsanity.com/paper/2404.00254/) (2024)

## Abstract (arXiv)

Graph neural networks (GNNs) have emerged as powerful tools for learning protein structures by capturing spatial relationships at the residue level. However, existing GNN-based methods often face challenges in learning multiscale representations and modeling long-range dependencies efficiently. In this work, we propose an efficient multiscale graph-based learning framework tailored to proteins. Our proposed framework contains two crucial components: (1) It constructs a hierarchical graph representation comprising a collection of fine-grained subgraphs, each corresponding to a secondary structure motif (e.g., α-helices, β-strands, loops), and a single coarse-grained graph that connects these motifs based on their spatial arrangement and relative orientation. (2) It employs two GNNs for feature learning: the first operates within individual secondary motifs to capture local interactions, and the second models higher-level structural relationships across motifs. Our modular framework allows a flexible choice of GNN in each stage. Theoretically, we show that our hierarchical framework preserves the desired maximal expressiveness, ensuring no loss of critical structural information. Empirically, we demonstrate that integrating baseline GNNs into our multiscale framework remarkably improves prediction accuracy and reduces computational cost across various benchmarks.