基于大规模天然抗体数据集的深度学习实现快速、准确的抗体结构预测。
Fast, accurate antibody structure prediction from deep learning on massive set of natural antibodies.
机构信息
Program in Molecular Biophysics, The Johns Hopkins University, Baltimore, MD, 21218, USA.
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, 21218, USA.
出版信息
Nat Commun. 2023 Apr 25;14(1):2389. doi: 10.1038/s41467-023-38063-x.
Antibodies have the capacity to bind a diverse set of antigens, and they have become critical therapeutics and diagnostic molecules. The binding of antibodies is facilitated by a set of six hypervariable loops that are diversified through genetic recombination and mutation. Even with recent advances, accurate structural prediction of these loops remains a challenge. Here, we present IgFold, a fast deep learning method for antibody structure prediction. IgFold consists of a pre-trained language model trained on 558 million natural antibody sequences followed by graph networks that directly predict backbone atom coordinates. IgFold predicts structures of similar or better quality than alternative methods (including AlphaFold) in significantly less time (under 25 s). Accurate structure prediction on this timescale makes possible avenues of investigation that were previously infeasible. As a demonstration of IgFold's capabilities, we predicted structures for 1.4 million paired antibody sequences, providing structural insights to 500-fold more antibodies than have experimentally determined structures.
抗体具有结合多种抗原的能力,它们已成为关键的治疗和诊断分子。抗体的结合是通过一组六个高变环来实现的,这些环通过遗传重组和突变而多样化。即使有了最近的进展,这些环的准确结构预测仍然是一个挑战。在这里,我们提出了 IgFold,这是一种用于抗体结构预测的快速深度学习方法。IgFold 由一个经过 5.58 亿个自然抗体序列训练的预训练语言模型组成,然后是直接预测骨干原子坐标的图网络。IgFold 预测的结构质量与替代方法(包括 AlphaFold)相似或更好,但所需时间明显更短(不到 25 秒)。在这个时间尺度上进行准确的结构预测使得以前不可行的研究途径成为可能。作为 IgFold 能力的演示,我们预测了 140 万个配对抗体序列的结构,为 500 倍以上的抗体提供了结构见解,这些抗体的结构以前尚未通过实验确定。