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深度学习在药物发现中的虚拟筛选加速流水线。

Deep learning pipeline for accelerating virtual screening in drug discovery.

机构信息

Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, 35000, Pakistan.

Integrative Omics and Molecular Modeling Laboratory, Department of Bioinformatics and Biotechnology, Government College University Faisalabad (GCUF), Faisalabad, 38000, Pakistan.

出版信息

Sci Rep. 2024 Nov 16;14(1):28321. doi: 10.1038/s41598-024-79799-w.

Abstract

In the race to combat ever-evolving diseases, the drug discovery process often faces the hurdles of high-cost and time-consuming procedures. To tackle these challenges and enhance the efficiency of identifying new therapeutic agents, we introduce VirtuDockDL, which is a streamlined Python-based web platform utilizing deep learning for drug discovery. This pipeline employs a Graph Neural Network to analyze and predict the effectiveness of various compounds as potential drug candidates. During the validation phase, VirtuDockDL was instrumental in identifying non-covalent inhibitors against the VP35 protein of the Marburg virus, a critical target given the virus's high fatality rate and limited treatment options. Further, in benchmarking, VirtuDockDL achieved 99% accuracy, an F1 score of 0.992, and an AUC of 0.99 on the HER2 dataset, surpassing DeepChem (89% accuracy) and AutoDock Vina (82% accuracy). Compared to RosettaVS, MzDOCK, and PyRMD, VirtuDockDL outperformed them by combining both ligand- and structure-based screening with deep learning. While RosettaVS excels in accurate docking but lacks high-throughput screening, and PyRMD focuses on ligand-based methods without AI integration, VirtuDockDL offers superior predictive accuracy and full automation for large-scale datasets, making it ideal for comprehensive drug discovery workflows. These results underscore the tool's capability to identify high-affinity inhibitors accurately across various targets, including the HER2 protein for cancer therapy, TEM-1 beta-lactamase for bacterial infections, and the CYP51 enzyme for fungal infections like Candidiasis. To sum up, VirtuDockDL combines user-friendly interface design with powerful computational capabilities to facilitate rapid, cost-effective drug discovery and development. The integration of AI in drug discovery could potentially transform the landscape of pharmaceutical research, providing faster responses to global health challenges. The VirtuDockDL is available at https://github.com/FatimaNoor74/VirtuDockDL .

摘要

在与不断演变的疾病作斗争的过程中,药物发现过程常常面临高成本和耗时程序的障碍。为了应对这些挑战并提高识别新治疗剂的效率,我们引入了 VirtuDockDL,这是一个基于 Python 的简化网络平台,利用深度学习进行药物发现。该管道使用图神经网络分析和预测各种化合物作为潜在药物候选物的有效性。在验证阶段,VirtuDockDL 在识别针对马尔堡病毒 VP35 蛋白的非共价抑制剂方面发挥了重要作用,鉴于该病毒的高死亡率和有限的治疗选择,该蛋白是一个关键靶标。此外,在基准测试中,VirtuDockDL 在 HER2 数据集上实现了 99%的准确率、0.992 的 F1 分数和 0.99 的 AUC,超过了 DeepChem(89%的准确率)和 AutoDock Vina(82%的准确率)。与 RosettaVS、MzDOCK 和 PyRMD 相比,VirtuDockDL 通过将配体和基于结构的筛选与深度学习相结合,表现更为出色。虽然 RosettaVS 在准确对接方面表现出色,但缺乏高通量筛选,而 PyRMD 则专注于基于配体的方法,不集成 AI,但 VirtuDockDL 提供了针对大规模数据集的更高预测准确性和完全自动化,非常适合全面的药物发现工作流程。这些结果强调了该工具在识别各种靶标(包括用于癌症治疗的 HER2 蛋白、用于细菌感染的 TEM-1 内酰胺酶以及用于真菌感染如念珠菌病的 CYP51 酶)的高亲和力抑制剂方面的能力。总之,VirtuDockDL 将用户友好的界面设计与强大的计算能力相结合,以促进快速、具有成本效益的药物发现和开发。人工智能在药物发现中的集成有可能彻底改变药物研究的格局,为应对全球健康挑战提供更快的反应。VirtuDockDL 可在 https://github.com/FatimaNoor74/VirtuDockDL 获得。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed99/11569207/7e11e654a59e/41598_2024_79799_Fig1_HTML.jpg

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