High-Throughput Virtual Screening of Small Molecule Inhibitors for SARS-CoV-2 Protein Targets with Deep Fusion Models
Lawrence Livermore National Laboratory（劳伦斯利弗莫尔国家实验室）；Sandia National Laboratories（桑迪亚国家实验室）；NVIDIA Corporation（英伟达公司）
Garrett A. Stevenson, Derek Jones, Hyojin Kim, W. F. Drew Bennett, Brian J. Bennion, Monica Borucki, Feliza Bourguet, Aidan Epstein, Magdalena Franco, Brooke Ha… 展开作者
Garrett A. Stevenson, Derek Jones, Hyojin Kim, W. F. Drew Bennett, Brian J. Bennion, Monica Borucki, Feliza Bourguet, Aidan Epstein, Magdalena Franco, Brooke Harmon, Stewart He, Max P. Katz, Daniel Kirshner, Victoria Lao, Edmond Y. Lau, Jacky Lo, Kevin McLoughlin, Richard Mosesso, Deepa K. Murugesh, Oscar A. Negrete, Edwin A. Saada, Brent Segelke, Maxwell Stefan, Marisa W. Torres, Dina Weilhammer, Sergio Wong, Yue Yang, Adam Zemla, Xiaohua Zhang, Fangqiang Zhu, Felice C. Lightstone, Jonathan E. Allen
Structure-based Deep Fusion models were recently shown to outperform several physics- and machine learning-based protein-ligand binding affinity prediction methods. As part of a multi-institutional COVID-19 pandemic response, over 500 million small molecules were computationally screened against four protein structures from the novel coronavirus (SARS-CoV-2), which causes COVID-19. Three enhancements to Deep Fusion were made in order to evaluate more than 5 billion docked poses on SARS-CoV-2 protein targets. First, the Deep Fusion concept was refined by formulating the architecture as one, coherently backpropagated model (Coherent Fusion) to improve binding-affinity prediction accuracy. Secondly, the model was trained using a distributed, genetic hyper-parameter optimization. Finally, a scalable, high-throughput screening capability was developed to maximize the number of ligands evaluated and expedite the path to experimental evaluation. In this work, we present both the methods developed for machine learning-based high-throughput screening and results from using our computational pipeline to find SARS-CoV-2 inhibitors.
Multi-view deep learning based molecule design and structural optimization accelerates the SARS-CoV-2 inhibitor discovery
School of Software, Shandong University（山东大学软件学院）；Joint SDU-NTU Centre for Artificial Intelligence Research (C-FAIR), Shandong University（山东大学-南洋理工大学人工智能联合研究中心（C-FAIR））；College of Intelligence and Computing, Tianjin University（天津大学智能与计算学部）
Large-scale ligand-based virtual screening for SARS-CoV-2 inhibitors using deep neural networks
ELLIS Unit at the LIT AI Lab, Johannes Kepler University Linz（林茨约翰内斯·开普勒大学 LIT AI 实验室 ELLIS 单元）；Institute for Machine Learning, Johannes Kepler University Linz（林茨约翰内斯·开普勒大学机器学习研究所）
A Novel Framework Integrating AI Model and Enzymological Experiments Promotes Identification of SARS-CoV-2 3CL Protease Inhibitors and Activity-based Probe
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences（中国科学院深圳先进技术研究院）；Shenzhen University Health Science Center（深圳大学医学部）
Active Learning-Guided Seq2Seq Variational Autoencoder for Multi-target Inhibitor Generation
Barcelona Supercomputing Center (BSC)（巴塞罗那超级计算中心）；PhD program in Biotechnology, Faculty of Pharmacy and Food Sciences, University of Barcelona (UB)（巴塞罗那大学药学与食品科学系生物技术博士项目）；Alzheimer's Research UK Oxford Drug Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, Oxford, UK（英国阿尔茨海默病研究奥德赛药物发现研究所、药物发现中心、医学系，牛津，英国）；Centre for Medicines Discovery, Nuffield Department of Medicine Research Building (NDMRB), University of Oxford, Oxford, UK（药物发现中心、医学系研究大楼（NDMRB）、牛津大学，牛津，英国）
Unraveling the Mechanism of Drug Binding to SARS-CoV-2 RNA Pseudoknot with Thermodynamics-Driven Machine Learning
Platform of Inter/Transdisciplinary Energy Research, Kyushu University（interdisciplinary 能源研究平台，九州大学）；Institute of Physics, Faculty of Physics, Astronomy and Informatics, Nicolaus Copernicus University（物理研究所，物理、天文学与信息学学院，尼古拉库普林大学）
Deep Neural Network-Based Prediction of B-Cell Epitopes for SARS-CoV and SARS-CoV-2: Enhancing Vaccine Design through Machine Learning
College of Agronomy and Biotechnology（农学与生物技术学院）；Accounting/Finance Department（会计与金融系）；Southwest University（西南大学）；Heritage Provider Network（遗产提供者网络）；Epocrates（Epocrates公司）；Athenahealth Inc.（雅典娜健康公司）
Deep learning forward and reverse primer design to detect SARS-CoV-2 emerging variants
University of Southampton（南安普顿大学）；Tohoku University Graduate School of Medicine（东北大学医学研究生院）；Tohoku University（东北大学）；University Hospital Southampton（南安普顿大学医院）
Fruit-CoV: An Efficient Vision-based Framework for Speedy Detection and Diagnosis of SARS-CoV-2 Infections Through Recorded Cough Sounds
Ton Duc Thang University（孙德胜大学）；ASICLAND（ASICLAND公司）；Sejong University（世宗大学）；Hanoi University of Industry（河内工业大学）；Northeastern University（东北大学）；Deakin University（迪肯大学）
Risk Estimation of SARS-CoV-2 Transmission from Bluetooth Low Energy Measurements
Fraunhofer Heinrich Hertz Institute（弗劳恩霍夫海因里希·赫兹研究所）；Technische Universität Berlin（柏林工业大学）；Korea University（高丽大学）；Max Planck Institute for Informatics（马克斯·普朗克信息学研究所）
Breath analysis by ultra-sensitive broadband laser spectroscopy detects SARS-CoV-2 infection
JILA（JILA研究所）；National Institute of Standards and Technology（美国国家标准与技术研究院）；University of Colorado（科罗拉多大学）；University of Basel（巴塞尔大学）；BioFrontiers Institute（生物前沿研究所）；University of Colorado Anschutz Medical Campus（科罗拉多大学安舒茨医学校区）
