The binding between proteins and ligands plays a crucial role in the realm of
drug discovery. Previous deep learning approaches have shown promising results
over traditional computationally intensive methods, but resulting in poor
generalization due to limited supervised data. In this paper, we propose to
learn protein-ligand binding representation in a self-supervised learning
manner. Different from existing pre-training approaches which treat proteins
and ligands individually, we emphasize to discern the intricate binding
patterns from fine-grained interactions. Specifically, this self-supervised
learning problem is formulated as a prediction of the conclusive binding
complex structure given a pocket and ligand with a Transformer based
interaction module, which naturally emulates the binding process. To ensure the
representation of rich binding information, we introduce two pre-training
tasks, i.e.~atomic pairwise distance map prediction and mask ligand
reconstruction, which comprehensively model the fine-grained interactions from
both structure and feature space. Extensive experiments have demonstrated the
superiority of our method across various binding tasks, including
protein-ligand affinity prediction, virtual screening and protein-ligand
docking.

我们提出了一种自监督学习的方法来学习蛋白质 - 配体结合表示，通过识别复杂的结合模式，从细粒度的相互作用中获得丰富的结合信息。我们的方法在各种结合任务中展现出优势，包括蛋白质 - 配体亲和性预测、虚拟筛选和蛋白质 - 配体对接。