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One-step Structure Prediction and Screening for Protein-Ligand Complexes using Multi-Task Geometric Deep Learning

2024/08/21 by Kelei He, Tiejun Dong, He, Kelei +5 · 1 citation
Biochemistry, Genetics and Molecular Biology · Computer Science · Medicine · #Artificial Intelligence (cs.AI) #Biomolecules (q-bio.BM) #Computational Drug Discovery Methods #FOS: Biological sciences #FOS: Computer and information sciences #Machine Learning (cs.LG) #Microbial Natural Products and Biosynthesis #Protein Structure and Dynamics

paper · pdf · doi:10.48550/arxiv.2408.11356

openalex publication_date 2024/08/21 · openalex created_date 2024/10/01 · openalex updated_date 2026/07/28

Abstract

Understanding the structure of the protein-ligand complex is crucial to drug development. Existing virtual structure measurement and screening methods are dominated by docking and its derived methods combined with deep learning. However, the sampling and scoring methodology have largely restricted the accuracy and efficiency. Here, we show that these two fundamental tasks can be accurately tackled with a single model, namely LigPose, based on multi-task geometric deep learning. By representing the ligand and the protein pair as a graph, LigPose directly optimizes the three-dimensional structure of the complex, with the learning of binding strength and atomic interactions as auxiliary tasks, enabling its one-step prediction ability without docking tools. Extensive experiments show LigPose achieved state-of-the-art performance on major tasks in drug research. Its considerable improvements indicate a promising paradigm of AI-based pipeline for drug development.

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