Pharmacophore and structure-based drug design, molecular dynamics and admet/tox studies to design novel potential pad4 inhibitors

Journal of Biomolecular Structure & Dynamics
Mariana P BarcellosCarlton A Taft

Abstract

We have used docking (GLIDE), pharmacophore modeling (Discovery Studio), long trajectory molecular dynamics (Discovery Studio) and ADMET/Tox (QikProp and DEREK) to investigate PAD4 in order to determine potential novel inhibitors and hits. We have carried out virtual screening in the ZINC natural compounds database. Pharmacokinetics and Toxicity of the best hits were assessed using databases implemented in softwares that create models based on chemical structures taking into account consideration about the toxicophoric groups. A wide variety of pharmaceutical relevant properties are determined in order to make decisions about molecular suitability. After screening and analysis, the 6 most promising PAD4 inhibitors are suggested, with strong interactions (pi-stacking, hydrogen bonds, hydrophobic contacts) and suitable pharmacotherapeutic profile as well.

References

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Oct 16, 2016·Journal of Biomolecular Structure & Dynamics·Carlos Henrique Tomich de Paula da Silva, Carlton Anthony Taft

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Citations

Jul 27, 2018·Journal of Biomolecular Structure & Dynamics·S R Shruti, R Rajasekaran
Jul 31, 2018·Journal of Biomolecular Structure & Dynamics·Kazeem O SulaimanSuaibu O Badmus
Aug 9, 2019·Journal of Biomolecular Structure & Dynamics·Sitrarasu Vijaya Prabhu, Sanjeev Kumar Singh
Jan 31, 2020·Journal of Biomolecular Structure & Dynamics·Shenjiao TangFangfang Wang
Apr 28, 2020·Journal of Biomolecular Structure & Dynamics·Cleydson B R SantosCarlos H T P Silva
Jan 6, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rosivaldo S BorgesCleydson B R Santos
Nov 5, 2020·Journal of Biomolecular Structure & Dynamics·Raimundo de A M NetoMadson R F Gomes
Nov 24, 2020·Molecular Informatics·Rıza ÖzçelikElif Ozkirimli
Aug 31, 2021·Journal of Biomolecular Structure & Dynamics·Muthu Kumar Thirunavukkarasu, Ramanathan Karuppasamy

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Software Mentioned

Lhasa Knowledge Suite
Biovia Discovery Studio
DEREK
GLIDE
OPLS3
OPLS2005
QikProp
CHARMm
Discovery Studio
Maestro

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