Efficient iterative virtual screening with Apache Spark and conformal prediction

Journal of Cheminformatics
Laeeq AhmedOla Spjuth

Abstract

Docking and scoring large libraries of ligands against target proteins forms the basis of structure-based virtual screening. The problem is trivially parallelizable, and calculations are generally carried out on computer clusters or on large workstations in a brute force manner, by docking and scoring all available ligands. In this study we propose a strategy that is based on iteratively docking a set of ligands to form a training set, training a ligand-based model on this set, and predicting the remainder of the ligands to exclude those predicted as 'low-scoring' ligands. Then, another set of ligands are docked, the model is retrained and the process is repeated until a certain model efficiency level is reached. Thereafter, the remaining ligands are docked or excluded based on this model. We use SVM and conformal prediction to deliver valid prediction intervals for ranking the predicted ligands, and Apache Spark to parallelize both the docking and the modeling. We show on 4 different targets that conformal prediction based virtual screening (CPVS) is able to reduce the number of docked molecules by 62.61% while retaining an accuracy for the top 30 hits of 94% on average and a speedup of 3.7. The implementation is available as ...Continue Reading

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Citations

Mar 8, 2019·Molecular Informatics·Mario LovrićRoman Kern
Mar 10, 2019·Bioinformatics·Payam Emami KhoonsariOla Spjuth
Sep 8, 2018·Journal of Cheminformatics·Ola Spjuth
Jun 1, 2021·Expert Opinion on Drug Discovery·Ola SpjuthAndreas Hellander
Jul 26, 2021·European Journal of Medicinal Chemistry·Victor T SabeHendrik G Kruger
Sep 1, 2020·Journal of Chemical Information and Modeling·Stanisław JastrzębskiSabina Podlewska
Oct 20, 2018·Journal of Chemical Information and Modeling·Isidro Cortés-Ciriano, Andreas Bender
Jul 2, 2020·ACS Central Science·Francesco GentileArtem Cherkasov
Jun 27, 2019·Journal of Chemical Information and Modeling·Isidro Cortés-Ciriano, Andreas Bender
Aug 22, 2018·Journal of Chemical Information and Modeling·Isidro Cortés-CirianoOliver Watson

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Software Mentioned

Spark
MPI
sparkhpc
SparkNow
Apache Hadoop
SureChEMBL
OEDocking
Google MapReduce
CPVS
Apache

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