AI is a viable alternative to high throughput screening: a 318-target study
Scientific Reports, vol. 14, pp. 7526
Abstract
High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery.
Authors 94
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Atomwise Inc., San Fransico, USA
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Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Affiliation as printed
Atomwise Inc., San Fransico, USA
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Amgen (United States) · Numerion Labs (United States)
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Atomwise Inc., San Fransico, USA
Amgen, Thousand Oaks, USA
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Amgen (United States) · OpenAI (United States)
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Amgen, Thousand Oaks, USA
OpenAI, San Francisco, USA
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OpenAI, San Francisco, USA
Model Medicines, La Jolla, USA
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Model Medicines, La Jolla, USA
Atomic.AI, San Francisco, USA
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Atomic.AI, San Francisco, USA
Edifice Health, Inc., San Mateo, USA
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Edifice Health, Inc., San Mateo, USA
METiS Therapeutics, Cambridge, USA
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METiS Therapeutics, Cambridge, USA
Genentech, San Mateo, USA
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Genentech · United States Navy
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Genentech, San Mateo, USA
US Navy Medical Service Corps Officer (2300/1810D), San Mateo, USA
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US Navy Medical Service Corps Officer (2300/1810D), San Mateo, USA
Totus Medicines, Inc., Emeryville, USA
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Totus Medicines, Inc., Emeryville, USA
Cytokinetics, Inc., South San Francisco, USA
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Cytokinetics (United States) · Nurix (United States)
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Cytokinetics, Inc., South San Francisco, USA
Nurix Therapeutics, San Francisco, USA
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Amazon (United States) · Nurix (United States)
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Nurix Therapeutics, San Francisco, USA
Amazon Alexa, Suite, USA
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Amazon Alexa, Suite, USA
The University of North Carolina at Chapel Hill Eshelman School of Pharmacy, Chapel Hill, USA
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University of North Carolina at Chapel Hill
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The University of North Carolina at Chapel Hill Eshelman School of Pharmacy, Chapel Hill, USA
Totus Medicines, Inc., Emeryville, USA
Refibered Inc., Cupertino, USA
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NVIDIA, Santa Clara, USA
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Harvard TH Chan School of Public Health, Boston, USA
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Instituto René Rachou-Fundação Oswaldo Cruz/Fiocruz Minas, Belo Horizonte, Brazil
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Instituto René Rachou-Fundação Oswaldo Cruz/Fiocruz Minas, Belo Horizonte, Brazil
Herbert Wertheim College of Medicine, Biomolecular Science Institute, Florida International University, Miami, USA
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Herbert Wertheim College of Medicine, Biomolecular Science Institute, Florida International University, Miami, USA
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Consejo Superior de Investigaciones Científicas · Centro Nacional de Biotecnología · University of Edinburgh
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Department of Plant Molecular Genetics, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain
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Consejo Superior de Investigaciones Científicas · Centro Nacional de Biotecnología · National Research Council
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Department of Plant Molecular Genetics, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain
CNR (Italian National Research Council), Rome, Italy
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