Dynamics based pharmacophore models for screening potential inhibitors of mycobacterial cyclopropane synthase

Journal of Chemical Information and Modeling
Chinmayee ChoudhuryG Narahari Sastry

Abstract

The therapeutic challenges in the treatment of tuberculosis demand multidisciplinary approaches for the identification of potential drug targets as well as fast and accurate techniques to screen huge chemical libraries. Mycobacterial cyclopropane synthase (CmaA1) has been shown to be essential for the survival of the bacteria due to its critical role in the synthesis of mycolic acids. The present study proposes pharmacophore models based on the structure of CmaA1 taking into account its various states in the cyclopropanation process, and their dynamic nature as assessed using molecular dynamics (MD) simulations. The qualities of these pharmacophore models were validated by mapping 23 molecules that have been previously reported to exhibit inhibitory activities on CmaA1. Additionally, 1398 compounds that have been shown to be inactive for tuberculosis were collected from the ChEMBL database and were screened against the models for validation. The models were further validated by comparing the results from pharmacophore mapping with the results obtained from docking these molecules with the respective protein structures. The best models are suggested by validating all the models based on their screening abilities and by comparing...Continue Reading

References

May 5, 1991·Journal of Molecular Biology·F Jiang, S H Kim
Jan 7, 1994·Journal of Molecular Biology·A R Leach
Mar 1, 1996·Journal of Molecular Recognition : JMR·D A GschwendI D Kuntz
Aug 28, 1998·Current Opinion in Biotechnology·L M Amzel
Jul 9, 1999·Journal of Molecular Recognition : JMR·M H Van Regenmortel
Jun 8, 2000·Journal of Medicinal Chemistry·H A CarlsonJ A McCammon
Aug 2, 2001·News in Physiological Sciences : an International Journal of Physiology Produced Jointly by the International Union of Physiological Sciences and the American Physiological Society·H R Bosshard
Jan 5, 2002·The Journal of Biological Chemistry·Chih-chin HuangJames C Sacchettini
Jan 16, 2002·Protein Science : a Publication of the Protein Society·Buyong MaRuth Nussinov
Jun 8, 2002·Current Pharmaceutical Design·Heather A Carlson
Jun 27, 2003·Journal of Medicinal Chemistry·Matthieu SchapiraMaxim Totrov
Mar 6, 2004·Journal of Molecular Biology·Claudio N Cavasotto, Ruben A Abagyan
Mar 20, 2004·Science·William L Jorgensen
Aug 4, 2004·Current Opinion in Chemical Biology·Hugo O VillarMark R Hansen
Sep 8, 2004·Current Opinion in Pharmacology·Tom L Blundell, S Patel
Oct 1, 2004·Journal of Medicinal Chemistry·Anna Maria FerrariBrian K Shoichet
Oct 14, 2004·Journal of the American Chemical Society·Kristin L Meagher, Heather A Carlson
Nov 3, 2004·Proteins·Kristin L Meagher, Heather A Carlson
Feb 16, 2006·Drug Discovery Today·Vickery L ArcusEdward N Baker
Jun 9, 2007·Journal of the American Chemical Society·Kelly L Damm, Heather A Carlson
Aug 19, 2007·Current Protein & Peptide Science·A Srinivas ReddyG Narahari Sastry
Sep 20, 2007·Journal of Chemical Information and Modeling·Michael G LernerHeather A Carlson
Feb 28, 2008·Current Opinion in Structural Biology·Maxim Totrov, Ruben Abagyan
Mar 21, 2008·Journal of Computational Chemistry·Sunhwan JoWonpil Im
Sep 19, 2008·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Szczepan JózefowskiKatarzyna Kwiatkowska
May 16, 2009·Journal of Computational Chemistry·B R BrooksM Karplus
Sep 19, 2009·Journal of Chemical Information and Modeling·Noeris K SalamWoody Sherman
Oct 21, 2009·Nature Chemical Biology·David D BoehrPeter E Wright
Nov 13, 2010·Trends in Molecular Medicine·Gyanu Lamichhane
Dec 15, 2010·Journal of Chemical Information and Modeling·Preethi Badrinarayan, G Narahari Sastry
Nov 11, 2011·PloS One·Praveen AnandNagasuma Chandra
Feb 7, 2012·Journal of Molecular Graphics & Modelling·Preethi Badrinarayan, G Narahari Sastry
May 10, 2012·Quarterly Reviews of Biophysics·Katrina W Lexa, Heather A Carlson
Nov 14, 2012·Journal of Chemical Information and Modeling·K VanommeslaegheA D MacKerell
Dec 25, 2012·Current Pharmaceutical Design·Preethi Badrinarayan, G Narahari Sastry
Oct 1, 1995·Annual Review of Physical Chemistry·S Hayward, N Go

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Citations

Jan 20, 2016·Biochemical and Biophysical Research Communications·Marcus WiederThierry Langer
Feb 4, 2016·Chemical Reviews·A Subha Mahadevi, G Narahari Sastry
Jul 9, 2016·European Journal of Medicinal Chemistry·Hany S IbrahimHatem A Abdel-Aziz
Jan 11, 2017·Journal of Chemical Information and Modeling·Marcus WiederThierry Langer
Nov 2, 2018·International Journal of Molecular Sciences·Ashutosh SrivastavaFlorence Tama
Nov 24, 2019·International Journal of Molecular Sciences·Pavel PolishchukTimur Madzhidov
Oct 20, 2017·Journal of Computer-aided Molecular Design·Phani Ghanakota, Heather A Carlson
Jan 12, 2021·Frontiers in Molecular Biosciences·Garon ArthurLanger Thierry
Jan 25, 2021·Current Opinion in Structural Biology·Rojan ShresthaAndras Fiser
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Serena VittorioLaura De Luca
Aug 5, 2018·Journal of Chemical Theory and Computation·Doris A SchuetzThierry Langer
Sep 2, 2021·Molecular Diversity·Sita Sirisha MadugulaG Narahari Sastry

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