# MSCoD: An Enhanced Bayesian Updating Framework with Multi-Scale Information Bottleneck and Cooperative Attention for Structure-Based Drug Design

arXiv: https://arxiv.org/abs/2509.25225 · HTML: https://mlsanity.com/paper/2509.25225/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 17 of its 37 references that are in the map.
- First posted on arXiv 24 Sep 2025.

## Builds on (most cited first, 17 of 17)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Swin-Unet: Unet-like Pure Transformer for Medical Image Segmentation](https://mlsanity.com/paper/2105.05537/) (2021)
- [Structure-based Drug Design with Equivariant Diffusion Models](https://mlsanity.com/paper/2210.13695/) (2022)
- [Pocket2Mol: Efficient Molecular Sampling Based on 3D Protein Pockets](https://mlsanity.com/paper/2205.07249/) (2022)
- [3D Equivariant Diffusion for Target-Aware Molecule Generation and Affinity Prediction](https://mlsanity.com/paper/2303.03543/) (2023)
- [A 3D Generative Model for Structure-Based Drug Design](https://mlsanity.com/paper/2203.10446/) (2022)
- [Generating 3D Molecules for Target Protein Binding](https://mlsanity.com/paper/2204.09410/) (2022)
- [How Does Information Bottleneck Help Deep Learning?](https://mlsanity.com/paper/2305.18887/) (2023)
- [DecompDiff: Diffusion Models with Decomposed Priors for Structure-Based Drug Design](https://mlsanity.com/paper/2403.07902/) (2024)
- [Generating 3D Molecules Conditional on Receptor Binding Sites with Deep Generative Models](https://mlsanity.com/paper/2110.15200/) (2021)
- [MolCRAFT: Structure-Based Drug Design in Continuous Parameter Space](https://mlsanity.com/paper/2404.12141/) (2024)
- [Structure-based drug design with geometric deep learning](https://mlsanity.com/paper/2210.11250/) (2022)
- [A Survey of Generative AI for de novo Drug Design: New Frontiers in Molecule and Protein Generation](https://mlsanity.com/paper/2402.08703/) (2024)
- [Zero-Shot 3D Drug Design by Sketching and Generating](https://mlsanity.com/paper/2209.13865/) (2022)
- [Structure-based drug design by denoising voxel grids](https://mlsanity.com/paper/2405.03961/) (2024)
- [t-SMILES: A Scalable Fragment-based Molecular Representation Framework for De Novo Molecule Generation](https://mlsanity.com/paper/2301.01829/) (2023)
- [Binding-Adaptive Diffusion Models for Structure-Based Drug Design](https://mlsanity.com/paper/2402.18583/) (2024)

## Abstract (arXiv)

Structure-Based Drug Design (SBDD) is a powerful strategy in computational drug discovery, utilizing three-dimensional protein structures to guide the design of molecules with improved binding affinity. However, capturing complex protein-ligand interactions across multiple scales remains challenging, as current methods often overlook the hierarchical organization and intrinsic asymmetry of these interactions. To address these limitations, we propose MSCoD, a novel Bayesian updating-based generative framework for structure-based drug design. In our MSCoD, Multi-Scale Information Bottleneck (MSIB) was developed, which enables semantic compression at multiple abstraction levels for efficient hierarchical feature extraction. Furthermore, a multi-head cooperative attention (MHCA) mechanism was developed, which employs asymmetric protein-to-ligand attention to capture diverse interaction types while addressing the dimensionality disparity between proteins and ligands. Empirical studies showed that MSCoD outperforms state-of-the-art methods on the benchmark dataset. Its real-world applicability is confirmed by case studies on difficult targets like KRAS G12D (7XKJ). Additionally, the MSIB and MHCA modules prove transferable, boosting the performance of GraphDTA on standard drug target affinity prediction benchmarks (Davis and Kiba). The code and data underlying this article are freely available at https://github.com/xulong0826/MSCoD.