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利用基于结构的深度学习解决对接姿势选择问题:最新进展、挑战与机遇

Addressing docking pose selection with structure-based deep learning: Recent advances, challenges and opportunities.

作者信息

Vittorio Serena, Lunghini Filippo, Morerio Pietro, Gadioli Davide, Orlandini Sergio, Silva Paulo, Pedretti Alessandro, Bonanni Domenico, Del Bue Alessio, Palermo Gianluca, Vistoli Giulio, Beccari Andrea R

机构信息

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Luigi Mangiagalli 25, I-20133 Milano, Italy.

EXSCALATE, Dompé Farmaceutici SpA, Via Tommaso de Amicis 95, 80123 Naples, Italy.

出版信息

Comput Struct Biotechnol J. 2024 May 18;23:2141-2151. doi: 10.1016/j.csbj.2024.05.024. eCollection 2024 Dec.

Abstract

Molecular docking is a widely used technique in drug discovery to predict the binding mode of a given ligand to its target. However, the identification of the near-native binding pose in docking experiments still represents a challenging task as the scoring functions currently employed by docking programs are parametrized to predict the binding affinity, and, therefore, they often fail to correctly identify the ligand native binding conformation. Selecting the correct binding mode is crucial to obtaining meaningful results and to conveniently optimizing new hit compounds. Deep learning (DL) algorithms have been an area of a growing interest in this sense for their capability to extract the relevant information directly from the protein-ligand structure. Our review aims to present the recent advances regarding the development of DL-based pose selection approaches, discussing limitations and possible future directions. Moreover, a comparison between the performances of some classical scoring functions and DL-based methods concerning their ability to select the correct binding mode is reported. In this regard, two novel DL-based pose selectors developed by us are presented.

摘要

分子对接是药物研发中广泛使用的一种技术,用于预测给定配体与其靶点的结合模式。然而,在对接实验中识别接近天然的结合构象仍然是一项具有挑战性的任务,因为目前对接程序所采用的评分函数是为预测结合亲和力而参数化的,因此,它们常常无法正确识别配体的天然结合构象。选择正确的结合模式对于获得有意义的结果以及方便地优化新的活性化合物至关重要。从这个意义上讲,深度学习(DL)算法因其能够直接从蛋白质 - 配体结构中提取相关信息而越来越受到关注。我们的综述旨在介绍基于深度学习的构象选择方法的最新进展,讨论其局限性和可能的未来方向。此外,还报告了一些经典评分函数和基于深度学习的方法在选择正确结合模式能力方面的性能比较。在这方面,展示了我们开发的两种基于深度学习的新型构象选择器。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/671c/11141151/278de81092ae/ga1.jpg

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