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Record W2995314362 · doi:10.1101/2019.12.15.877316

Deep Docking - a Deep Learning Approach for Virtual Screening of Big Chemical Datasets

2019· preprint· en· W2995314362 on OpenAlexafffund
Francesco Gentile, Vibudh Agrawal, Michael Hsing, Fuqiang Ban, Ulf Norinder, Martin Gleave, Artem Cherkasov

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2019
Typepreprint
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsUniversity of British Columbia
FundersCanadian Cancer Society Research Institute
KeywordsVirtual screeningWorkflowChemical databaseDrug discoveryDocking (animal)Computer scienceDeep learningBig dataArtificial intelligenceMachine learningData miningDatabaseBioinformaticsBiology

Abstract

fetched live from OpenAlex

ABSTRACT Drug discovery is an extensive and rigorous process that requires up to 2 billion dollars of investments and more than ten years of research and development to bring a molecule “from bench to a bedside”. While virtual screening can significantly enhance drug discovery workflow, it ultimately lags the current rate of expansion of chemical databases that already incorporate billions of purchasable compounds. This surge of available small molecules presents great opportunities for drug discovery but also demands for faster virtual screening methods and protocols. In order to address this challenge, we herein introduce Deep Docking ( D 2 ) - a novel deep learning-based approach which is suited for docking billions of molecular structures. The developed D 2 -platform utilizes quantitative structure-activity relationship (QSAR) based deep models trained on docking scores of subsets of a large chemical library (Big Base) to approximate the docking outcome for yet unprocessed molecular entries and to remove unfavorable structures in an iterative manner. We applied D 2 to virtually screen 1.36 billion molecules form the ZINC15 library against 12 prominent target proteins, and demonstrated up to 100-fold chemical data reduction and 6,000-fold enrichment for top hits, without notable loss of well-docked entities. The developed D 2 protocol can readily be used in conjunction with any docking program and was made publicly available.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Methods · Consensus signal: none
Teacher disagreement score0.499
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0030.003
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.027
GPT teacher head0.262
Teacher spread0.235 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designSimulation or modeling
Domainnot available
GenreMethods

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations11
Published2019
Admission routes2
Has abstractyes

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