How to Achieve Better Results Using PASS-Based Virtual Screening: Case Study for Kinase Inhibitors

Frontiers in Chemistry
Pavel V PogodinVladimir V Poroikov

Abstract

Discovery of new pharmaceutical substances is currently boosted by the possibility of utilization of the Synthetically Accessible Virtual Inventory (SAVI) library, which includes about 283 million molecules, each annotated with a proposed synthetic one-step route from commercially available starting materials. The SAVI database is well-suited for ligand-based methods of virtual screening to select molecules for experimental testing. In this study, we compare the performance of three approaches for the analysis of structure-activity relationships that differ in their criteria for selecting of "active" and "inactive" compounds included in the training sets. PASS (Prediction of Activity Spectra for Substances), which is based on a modified Naïve Bayes algorithm, was applied since it had been shown to be robust and to provide good predictions of many biological activities based on just the structural formula of a compound even if the information in the training set is incomplete. We used different subsets of kinase inhibitors for this case study because many data are currently available on this important class of drug-like molecules. Based on the subsets of kinase inhibitors extracted from the ChEMBL 20 database we performed the PA...Continue Reading

References

Dec 29, 2000·Journal of Chemical Information and Computer Sciences·V V PoroikovA Kos
Mar 20, 2004·Science·William L Jorgensen
Dec 17, 2004·Nature·Christopher Lipinski, Andrew Hopkins
Dec 27, 2005·Drug Discovery Today·Andreas P Russ, Stefan Lampel
Dec 13, 2006·Journal of Medicinal Chemistry·James H NettlesMeir Glick
Feb 10, 2007·Journal of Chemical Information and Modeling·Jean-François Truchon, Christopher I Bayly
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Oleg FedorovStefan Knapp
Feb 15, 2008·Journal of Computer-aided Molecular Design·John J Irwin
Jan 23, 2010·Nature Reviews. Cancer·Zachary A KnightKevan M Shokat
May 21, 2010·Accounts of Chemical Research·Robin S Bon, Herbert Waldmann
Jul 16, 2010·Journal of Nanobiotechnology·Selvaraj BarathmanikanthSangiliyandi Gurunathan
Oct 26, 2010·Drug Discovery Today·Qingliang LiStephen H Bryant
Mar 19, 2011·BMC Bioinformatics·Xavier RobinMarkus Müller
Jun 2, 2011·Nature Reviews. Drug Discovery·Fabio PammolliMassimo Riccaboni
Mar 1, 2012·Journal of Chemical Information and Modeling·Bin ChenJohannes H Voigt
Apr 21, 2012·Drug Discovery Today·Fabian López-VallejoJosé L Medina-Franco
Oct 24, 2012·Journal of Chemical Information and Modeling·Lars RuddigkeitJean-Louis Reymond
Nov 3, 2012·Current Topics in Medicinal Chemistry·Christian Kramer, Richard Lewis
Jan 24, 2013·Drug Discovery Today·José L Medina-FrancoRichard A Houghten
Apr 9, 2013·Journal of Cheminformatics·Sabina SmuszAndrzej J Bojarski
Oct 16, 2013·Journal of Chemical Information and Modeling·Zhi-Luo DengDe-Xin Kong
Oct 29, 2013·Journal of Chemical Information and Modeling·Pekka TiikkainenLutz Franke
Nov 8, 2013·Nucleic Acids Research·Yanli WangStephen H Bryant
Nov 10, 2013·Nucleic Acids Research·Vivian LawDavid S Wishart
Nov 12, 2013·Nucleic Acids Research·A Patrícia BentoJohn P Overington
Mar 1, 2014·Future Medicinal Chemistry·Jürgen Bajorath
Apr 2, 2014·Computational and Structural Biotechnology Journal·Ye HuJürgen Bajorath
Jul 1, 2014·Journal of Cheminformatics·Rafał KurczabAndrzej J Bojarski
May 24, 2015·Biochimica Et Biophysica Acta·Osman A GaniRichard A Engh
Jun 13, 2015·Journal of Cheminformatics·Avid M AfzalRobert C Glen
Jul 24, 2015·Journal of Computer-aided Molecular Design·George PapadatosJohn P Overington
Aug 26, 2015·SAR and QSAR in Environmental Research·P V PogodinV V Poroikov
Oct 1, 2015·ACS Chemical Biology·Sarah BarelierBrian K Shoichet
Oct 20, 2015·Journal of Chemical Information and Modeling·Teague Sterling, John J Irwin
Oct 21, 2015·Journal of Chemical Information and Modeling·Rosa BuonfiglioThierry Kogej
Oct 27, 2015·Journal of Cheminformatics·Lewis H MervinAndreas Bender
Oct 27, 2015·Nature Biotechnology·Jonathan M ElkinsWilliam J Zuercher
Nov 14, 2015·Journal of Computer-aided Molecular Design·Pavel SidorovDragos Horvath
Jan 13, 2016·Journal of Chemical Information and Modeling·Toshio Fujita, David A Winkler
Feb 26, 2016·Current Pharmaceutical Design·Antonino LauriaCarla Gentile
Apr 16, 2016·PloS One·Swarit JasialJürgen Bajorath
Apr 29, 2016·PLoS Computational Biology·Raul Rodriguez-Esteban
May 18, 2016·Expert Opinion on Drug Discovery·Aeri LeeDongsup Kim
Jun 10, 2016·Journal of Chemical Information and Modeling·Denis FourchesAlexander Tropsha
Dec 1, 2013·Molecular Informatics·Tuomo KalliokoskiAnna Vulpetti

❮ Previous
Next ❯

Citations

Oct 12, 2018·Anti-cancer Agents in Medicinal Chemistry·Rabia HameedShagufta Perveen
May 2, 2020·Chemical Society Reviews·Eugene N MuratovAlexander Tropsha
Sep 25, 2019·SAR and QSAR in Environmental Research·P V PogodinV V Poroikov
Nov 27, 2020·International Journal of Molecular Sciences·Oliwia KoszłaAgnieszka A Kaczor
Jan 27, 2021·Journal of Chemical Information and Modeling·Janosch Menke, Oliver Koch
Apr 4, 2021·Journal of Biomolecular Structure & Dynamics·Nandan KumarG Narahari Sastry
May 21, 2021·Journal of Chemical Information and Modeling·Renan P O CostaMarcus T Scotti
Oct 31, 2019·Journal of Chemical Information and Modeling·Pavel V PogodinVladimir V Poroikov

❮ Previous
Next ❯

Software Mentioned

Prediction of Activity Spectra for Substances ( PASS )
SQL
R
SAVI
PASS
ChEMBL
MySQL
R package pROC
R package
R package mlr

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.