Applying Machine Learning to Ultrafast Shape Recognition in Ligand-Based Virtual Screening

Frontiers in Pharmacology
Etienne Bonanno, Jean-Paul Ebejer

Abstract

Ultrafast Shape Recognition (USR), along with its derivatives, are Ligand-Based Virtual Screening (LBVS) methods that condense 3-dimensional information about molecular shape, as well as other properties, into a small set of numeric descriptors. These can be used to efficiently compute a measure of similarity between pairs of molecules using a simple inverse Manhattan Distance metric. In this study we explore the use of suitable Machine Learning techniques that can be trained using USR descriptors, so as to improve the similarity detection of potential new leads. We use molecules from the Directory for Useful Decoys-Enhanced to construct machine learning models based on three different algorithms: Gaussian Mixture Models (GMMs), Isolation Forests and Artificial Neural Networks (ANNs). We train models based on full molecule conformer models, as well as the Lowest Energy Conformations (LECs) only. We also investigate the performance of our models when trained on smaller datasets so as to model virtual screening scenarios when only a small number of actives are known a priori. Our results indicate significant performance gains over a state of the art USR-derived method, ElectroShape 5D, with GMMs obtaining a mean performance up to...Continue Reading

References

Jun 18, 2004·Combinatorial Chemistry & High Throughput Screening·Florence L Stahura, Jürgen Bajorath
Jul 25, 2006·Journal of Chemical Information and Modeling·Stéphane BetziXavier Morelli
Dec 13, 2006·Journal of Medicinal Chemistry·Niu HuangJohn J Irwin
Jan 6, 2007·Journal of Computer-aided Molecular Design·Beining ChenNikolaus Stiefl
Mar 8, 2007·Journal of Computational Chemistry·Pedro J Ballester, W Graham Richards
Feb 20, 2008·Chemistry Central Journal·Edward O CannonJohn B O Mitchell
Feb 4, 2009·Journal of Molecular Graphics & Modelling·Pedro J BallesterW Graham Richards
Feb 12, 2009·Chemical Biology & Drug Design·Adrian Schreyer, Tom Blundell
Oct 6, 2009·Journal of Molecular Graphics & Modelling·M Stuart ArmstrongW Graham Richards
Jul 9, 2010·Journal of Computer-aided Molecular Design·M Stuart ArmstrongW Graham Richards
Jul 22, 2011·IEEE Transactions on Image Processing : a Publication of the IEEE Signal Processing Society·Turgay Celik, Tardi Tjahjadi
Aug 9, 2011·Journal of Chemical Information and Modeling·Xiaofeng LiuHonglin Li
Aug 9, 2011·Journal of Computer-aided Molecular Design·M Stuart ArmstrongW Graham Richards
Apr 10, 2012·Journal of Chemical Information and Modeling·Jean-Paul EbejerCharlotte M Deane
Jun 22, 2012·Journal of Medicinal Chemistry·Michael M MysingerBrian K Shoichet
Nov 8, 2012·Journal of Cheminformatics·Adrian M Schreyer, Tom Blundell
May 9, 2013·Current Medicinal Chemistry·A Lavecchia, C Di Giovanni
Dec 3, 2014·Drug Discovery Today·Antonio Lavecchia
Nov 18, 2015·Journal of Chemical Information and Modeling·Sereina Riniker, Gregory Landrum
Mar 2, 2016·Journal of Health Economics·Joseph A DiMasiRonald W Hansen
Apr 26, 2016·Wiley Interdisciplinary Reviews. Computational Molecular Science·Qurrat Ul AinPedro J Ballester
May 17, 2010·Molecular Informatics·Andreas JahnAndreas Zell
Apr 26, 2017·Scientific Reports·Maciej WójcikowskiPawel Siedlecki

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Citations

Apr 21, 2021·Angewandte Chemie·Martyna MoskalBartosz A Grzybowski

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Methods Mentioned

BETA
X-ray

Software Mentioned

AWS Educate
DUD
USR
Scikit
Keras
MolVS
Amazon
ESshape3D
USRCAT
ElectroShape

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