论文标题

目标感知分子图生成

Target-aware Molecular Graph Generation

论文作者

Tan, Cheng, Gao, Zhangyang, Li, Stan Z.

论文摘要

具有所需生物活性的分子产生的分子吸引了越来越多的药物发现。以前的分子生成模型被设计为化学中心方法,几乎​​不考虑药物目标相互作用,从而限制了它们的实际应用。在本文中,我们旨在以桥接生物学活性和分子设计的目标感知方式产生分子药物。为了解决此问题,我们从几个公开可用数据集中编译了一个基准数据集,并在统一框架中构建基准。在基于流动分子生成模型的最新优势的基础上,我们提出了Siamflow,该siamflow迫使流动以适合潜在空间中目标序列嵌入的分布。具体而言,我们采用比对损失和统一的损失,将目标序列嵌入和药物图嵌入到协议中,同时避免崩溃。此外,我们通过学习目标序列嵌入的空间将对齐方式分为一对多问题。实验定量表明,我们提出的方法在潜在的靶向分子图生成的潜在空间中学习有意义的表示,并为药物发现中提供了桥梁生物学和化学的替代方法。

Generating molecules with desired biological activities has attracted growing attention in drug discovery. Previous molecular generation models are designed as chemocentric methods that hardly consider the drug-target interaction, limiting their practical applications. In this paper, we aim to generate molecular drugs in a target-aware manner that bridges biological activity and molecular design. To solve this problem, we compile a benchmark dataset from several publicly available datasets and build baselines in a unified framework. Building on the recent advantages of flow-based molecular generation models, we propose SiamFlow, which forces the flow to fit the distribution of target sequence embeddings in latent space. Specifically, we employ an alignment loss and a uniform loss to bring target sequence embeddings and drug graph embeddings into agreements while avoiding collapse. Furthermore, we formulate the alignment into a one-to-many problem by learning spaces of target sequence embeddings. Experiments quantitatively show that our proposed method learns meaningful representations in the latent space toward the target-aware molecular graph generation and provides an alternative approach to bridge biology and chemistry in drug discovery.

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