论文标题
Equibind:药物结合结构预测的几何深度学习
EquiBind: Geometric Deep Learning for Drug Binding Structure Prediction
论文作者
论文摘要
预测药物样分子如何与特定蛋白靶靶标结合是药物发现中的核心问题。一种非常快速的计算结合方法将启用关键应用程序,例如快速虚拟筛查或药物工程。现有的方法在计算上很昂贵,因为它们依赖于重型候选抽样以及评分,排名和微调步骤。我们用Equibind,SE(3) - 等级的几何深度学习模型对i)进行直接拍摄的预测i)受体结合位置(盲码)和ii)配体的结合姿势和方向来挑战这种范式。与传统和最近的基线相比,Equibind实现了巨大的加速和质量更高的质量。此外,当将其与现有的微调技术耦合时,我们以增加运行时间为代价时会显示出额外的改进。最后,我们提出了一个新颖而快速的微调模型,该模型基于von Mises Angular距离的封闭形式的全局最小值,以调整配体可旋转键的扭转角度到给定的输入原子云,避免以前昂贵的差异进化策略,以使能量最小化。
Predicting how a drug-like molecule binds to a specific protein target is a core problem in drug discovery. An extremely fast computational binding method would enable key applications such as fast virtual screening or drug engineering. Existing methods are computationally expensive as they rely on heavy candidate sampling coupled with scoring, ranking, and fine-tuning steps. We challenge this paradigm with EquiBind, an SE(3)-equivariant geometric deep learning model performing direct-shot prediction of both i) the receptor binding location (blind docking) and ii) the ligand's bound pose and orientation. EquiBind achieves significant speed-ups and better quality compared to traditional and recent baselines. Further, we show extra improvements when coupling it with existing fine-tuning techniques at the cost of increased running time. Finally, we propose a novel and fast fine-tuning model that adjusts torsion angles of a ligand's rotatable bonds based on closed-form global minima of the von Mises angular distance to a given input atomic point cloud, avoiding previous expensive differential evolution strategies for energy minimization.