AI is a viable alternative to high throughput screening: a 318-target study.

dc.contributor.author

Atomwise AIMS Program

dc.date.accessioned

2024-06-01T13:56:45Z

dc.date.available

2024-06-01T13:56:45Z

dc.date.issued

2024-04

dc.description.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.

dc.identifier

10.1038/s41598-024-54655-z

dc.identifier.issn

2045-2322

dc.identifier.issn

2045-2322

dc.identifier.uri

https://hdl.handle.net/10161/30749

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Scientific reports

dc.relation.isversionof

10.1038/s41598-024-54655-z

dc.rights.uri

https://creativecommons.org/licenses/by-nc/4.0

dc.subject

Atomwise AIMS Program

dc.subject

Small Molecule Libraries

dc.subject

Drug Discovery

dc.subject

High-Throughput Screening Assays

dc.title

AI is a viable alternative to high throughput screening: a 318-target study.

dc.type

Journal article

pubs.begin-page

7526

pubs.issue

1

pubs.organisational-group

Duke

pubs.organisational-group

School of Medicine

pubs.organisational-group

Trinity College of Arts & Sciences

pubs.organisational-group

Basic Science Departments

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

Biochemistry

pubs.organisational-group

Pathology

pubs.organisational-group

Duke Cancer Institute

pubs.organisational-group

Chemistry

pubs.publication-status

Published

pubs.volume

14

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