论文标题

COSP:手袋和配体的共同监督预处理

CoSP: Co-supervised pretraining of pocket and ligand

论文作者

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

论文摘要

我们可以将袖珍配体的相互作用知识注入预训练的模型并共同学习其化学空间吗?近年来,预处理的分子和蛋白质引起了很大的关注,而这些方法中的大多数都集中在学习一个化学空间,并且缺乏注射生物学知识。我们提出了一个共同监督预告片(COSP)的框架,以同时学习3D口袋和配体表示。我们使用封闭式的几何消息传递层来对3D口袋和配体进行建模,其中每个节点的化学特征,几何位置和方向都被考虑。为了学习生物学有意义的嵌入,我们通过对比度损失将袖珍配体相互作用知识注入预处理模型。考虑到分子的特异性,我们进一步提出了化学相似性增强的负抽样策略,以提高对比度学习绩效。通过广泛的实验,我们得出的结论是,COSP可以在口袋匹配,分子属性预测和虚拟筛选中获得竞争成果。

Can we inject the pocket-ligand interaction knowledge into the pre-trained model and jointly learn their chemical space? Pretraining molecules and proteins has attracted considerable attention in recent years, while most of these approaches focus on learning one of the chemical spaces and lack the injection of biological knowledge. We propose a co-supervised pretraining (CoSP) framework to simultaneously learn 3D pocket and ligand representations. We use a gated geometric message passing layer to model both 3D pockets and ligands, where each node's chemical features, geometric position and orientation are considered. To learn biological meaningful embeddings, we inject the pocket-ligand interaction knowledge into the pretraining model via contrastive loss. Considering the specificity of molecules, we further propose a chemical similarity-enhanced negative sampling strategy to improve the contrastive learning performance. Through extensive experiments, we conclude that CoSP can achieve competitive results in pocket matching, molecule property predictions, and virtual screening.

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