arXiv:2511.15906cs.LGq-bio.BM2025-11NeurIPS被引 2

用神经场统一生成各类分子,条件可控且性能优秀。

Unified all-atom molecule generation with neural fields

  • 基于神经场建模分子为连续原子密度,支持跨模态生成。
  • 在小分子、环肽和抗体结合区生成上达到领先水平。
  • 适合药物设计中从头生成抗体和复杂分子的科研人员使用。

面向结构的药物设计生成模型通常局限于特定模态,限制了应用范围。为此,我们提出FuncBind框架,利用计算机视觉技术生成目标结构条件下的全原子分子,覆盖不同原子系统。FuncBind采用神经场表示分子为连续原子密度,并结合源自计算机视觉的现代得分生成模型。该模态无关表示使单一统一模型可训练于从小分子到大分子的多样化系统,支持可变原子/残基数量,包括非标准氨基酸。FuncBind在小分子、大环肽及抗体互补决定区环的生成任务中表现优异。此外,通过重新设计两个共晶结构的互补决定区H3环,成功生成体外验证的新型抗体结合剂。最后,我们构建了一个新的数据集与基准,用于结构条件下的大环肽生成。代码已公开于https://github.com/prescient-design/funcbind。

原文摘要 · Abstract (English)

Generative models for structure-based drug design are often limited to a specific modality, restricting their broader applicability. To address this challenge, we introduce FuncBind, a framework based on computer vision to generate target-conditioned, all-atom molecules across atomic systems. FuncBind uses neural fields to represent molecules as continuous atomic densities and employs score-based generative models with modern architectures adapted from the computer vision literature. This modality-agnostic representation allows a single unified model to be trained on diverse atomic systems, from small to large molecules, and handle variable atom/residue counts, including non-canonical amino acids. FuncBind achieves competitive in silico performance in generating small molecules, macrocyclic peptides, and antibody complementarity-determining region loops, conditioned on target structures. FuncBind also generated in vitro novel antibody binders via de novo redesign of the complementarity-determining region H3 loop of two chosen co-crystal structures. As a final contribution, we introduce a new dataset and benchmark for structure-conditioned macrocyclic peptide generation. The code is available at https://github.com/prescient-design/funcbind.

分子生成神经场抗体设计药物发现

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