论文标题

E3BIND:用于蛋白质码头对接的端到端的模棱两可的网络

E3Bind: An End-to-End Equivariant Network for Protein-Ligand Docking

论文作者

Zhang, Yangtian, Cai, Huiyu, Shi, Chence, Zhong, Bozitao, Tang, Jian

论文摘要

在对给定蛋白靶标的配体结合姿势的硅硅预测中,在药物发现中是至关重要但具有挑战性的任务。这项工作的重点是盲目的灵活自我折叠,我们旨在预测对接分子的位置,方向和构象。传统的基于物理的方法通常会遭受评分功能不准确和推理成本高。最近,由于推断和有希望的表现,基于深度学习技术的数据驱动方法引起了人们的兴趣。这些方法通常通过首先预测蛋白质和配体之间的距离,然后根据预测的距离生成最终坐标,或者直接预测配体的全局旋转旋转译出来采用两阶段方法。在本文中,我们采取了另一条路线。受Alphafold2对蛋白质结构预测的振奋人心的启发,我们提出了E3Bind,这是一个端到端的exteremiant网络,它迭代地更新了配体姿势。 E3BIND通过仔细考虑对接和结合位点的局部环境中的几何约束来对蛋白质 - 配体相互作用进行建模。标准基准数据集上的实验证明了与传统和最近提供的深度学习方法相比,我们的端到端训练模型的出色性能。

In silico prediction of the ligand binding pose to a given protein target is a crucial but challenging task in drug discovery. This work focuses on blind flexible selfdocking, where we aim to predict the positions, orientations and conformations of docked molecules. Traditional physics-based methods usually suffer from inaccurate scoring functions and high inference cost. Recently, data-driven methods based on deep learning techniques are attracting growing interest thanks to their efficiency during inference and promising performance. These methods usually either adopt a two-stage approach by first predicting the distances between proteins and ligands and then generating the final coordinates based on the predicted distances, or directly predicting the global roto-translation of ligands. In this paper, we take a different route. Inspired by the resounding success of AlphaFold2 for protein structure prediction, we propose E3Bind, an end-to-end equivariant network that iteratively updates the ligand pose. E3Bind models the protein-ligand interaction through careful consideration of the geometric constraints in docking and the local context of the binding site. Experiments on standard benchmark datasets demonstrate the superior performance of our end-to-end trainable model compared to traditional and recently-proposed deep learning methods.

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