arXiv:2608.01007cs.LG2026-08

融合双靶点信息生成高亲和力分子,提升复杂疾病药物设计效率。

Fused Bayesian Flow Networks for Dual-Target Molecular Design

论文配图:Fused Bayesian Flow Networks for Dual-Target Molecular Design
图 1 · 摘自论文原文
  • 通过分布融合与专家乘积机制,统一建模双靶点特征
  • 在真实数据上实现双靶点结合亲和力提升,分子性质优良
  • 适合新药研发人员探索多靶点药物设计

双靶点药物设计旨在生成可同时作用于两个靶蛋白的三维分子,为复杂疾病发现多药理化合物提供有效路径。尽管现有生成模型在单靶点设计中表现良好,但当前双靶点方法或仅关注序列生成,或引入额外预测漂移项至基于扩散的生成轨迹,难以充分融合双靶点特征信息。本文提出FusedBFN,一种用于双靶点分子设计的融合贝叶斯流网络。FusedBFN将双靶点生成建模为统一连续参数空间中的分布融合问题,并采用专家乘积(product-of-experts)形式,在整个生成过程中整合双靶点信息。为应对双靶点结构数据稀缺问题,我们利用预训练的靶点感知贝叶斯流网络(target-aware BFN)作为共享主干。进一步提出基于化学先验的对齐方法与无先验口袋对齐策略,构建对齐的双靶点上下文。大量实验表明,FusedBFN生成的分子在双靶点上具有强结合亲和力,同时保持理想的分子属性。

原文摘要 · Abstract (English)

Dual-target drug design aims to generate 3D molecules that can simultaneously interact with two target proteins, offering a promising route for discovering polypharmacological compounds against complex diseases. While recent generative models have shown encouraging performance in single-target drug design, existing dual-target approaches either focus on sequence generation or introduce an additional predictive drift term into the diffusion-based generative trajectory, which limits their ability to fully integrate feature information from both targets. We propose FusedBFN, a fused Bayesian flow network (BFN) for dual-target molecular design. FusedBFN formulates dual-target generation as distribution fusion in a unified continuous parameter space and employs a product-of-experts formulation to incorporate dual-target information throughout the generative process. To address the scarcity of dual-target structural data, we leverage a pretrained target-aware BFN model as the shared backbone. We further introduce a chemically aware prior-based alignment method and a prior-free pocket alignment strategy to construct aligned dual-target contexts. Extensive experiments demonstrate that FusedBFN generates molecules with strong binding affinity toward dual targets while maintaining favorable molecular properties.

分子生成双靶点设计贝叶斯网络药物发现

Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。