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

• URL: http://arxiv.org/abs/2509.25225v1
• Date: Wed, 24 Sep 2025 10:51:07 GMT
• Title: MSCoD: An Enhanced Bayesian Updating Framework with Multi-Scale Information Bottleneck and Cooperative Attention for Structure-Based Drug Design
• Authors: Long Xu, Yongcai Chen, Fengshuo Liu, Yuzhong Peng,
• Abstract summary: We propose MSCoD, a novel Bayesian updating-based generative framework for structure-based drug design.<n>In our MSCoD, Multi-Scale Information Bottleneck (MSIB) was developed, which enables semantic compression at multiple abstraction levels.<n>MSCoD outperforms state-of-the-art methods on the benchmark dataset.
• Score: 2.4060611914774763
• License: http://arxiv.org/licenses/nonexclusive-distrib/1.0/
• Abstract: 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. Case studies on challenging targets such as KRAS G12D further demonstrate its applicability in real-world scenarios. The code and data underlying this article are freely available at https://github.com/xulong0826/MSCoD.

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