Huang Han, Sun Leilei, Du Bowen, Lv Weifeng
IEEE Trans Neural Netw Learn Syst. 2024 Sep;35(9):11857-11871. doi: 10.1109/TNNLS.2024.3416328. Epub 2024 Sep 3.
Designing new molecules is essential for drug discovery and material science. Recently, deep generative models that aim to model molecule distribution have made promising progress in narrowing down the chemical research space and generating high-fidelity molecules. However, current generative models only focus on modeling 2-D bonding graphs or 3-D geometries, which are two complementary descriptors for molecules. The lack of ability to jointly model them limits the improvement of generation quality and further downstream applications. In this article, we propose a joint 2-D and 3-D graph diffusion model (JODO) that generates geometric graphs representing complete molecules with atom types, formal charges, bond information, and 3-D coordinates. To capture the correlation between 2-D molecular graphs and 3-D geometries in the diffusion process, we develop a diffusion graph transformer (DGT) to parameterize the data prediction model that recovers the original data from noisy data. The DGT uses a relational attention mechanism that enhances the interaction between node and edge representations. This mechanism operates concurrently with the propagation and update of scalar attributes and geometric vectors. Our model can also be extended for inverse molecular design targeting single or multiple quantum properties. In our comprehensive evaluation pipeline for unconditional joint generation, the experimental results show that JODO remarkably outperforms the baselines on the QM9 and GEOM-Drugs datasets. Furthermore, our model excels in few-step fast sampling, as well as in inverse molecule design and molecular graph generation. Our code is provided in https://github.com/GRAPH-0/JODO.
设计新分子对于药物发现和材料科学至关重要。最近,旨在对分子分布进行建模的深度生成模型在缩小化学研究空间和生成高保真分子方面取得了有前景的进展。然而,当前的生成模型仅专注于对二维键合图或三维几何结构进行建模,而这两者是分子的两个互补描述符。缺乏对它们进行联合建模的能力限制了生成质量的提高以及进一步的下游应用。在本文中,我们提出了一种二维和三维联合图扩散模型(JODO),该模型生成表示完整分子的几何图,包括原子类型、形式电荷、键信息和三维坐标。为了在扩散过程中捕捉二维分子图和三维几何结构之间的相关性,我们开发了一种扩散图变换器(DGT)来参数化从噪声数据中恢复原始数据的数据预测模型。DGT使用关系注意力机制来增强节点和边表示之间的相互作用。该机制与标量属性和几何向量的传播和更新同时运行。我们的模型还可以扩展用于针对单个或多个量子特性的逆分子设计。在我们用于无条件联合生成的综合评估管道中,实验结果表明JODO在QM9和GEOM - Drugs数据集上显著优于基线。此外,我们的模型在几步快速采样以及逆分子设计和分子图生成方面表现出色。我们的代码可在https://github.com/GRAPH-0/JODO获取。
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