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Structural insights of Staphylococcus aureus FtsZ inhibitors through molecular docking, 3D-QSAR and molecular dynamics simulations.
J Recept Signal Transduct Res. 2018 Feb; 38(1):61-70.JR

Abstract

Filamentous temperature-sensitive protein Z (FtsZ) is a protein encoded by the FtsZ gene that assembles into a Z-ring at the future site of the septum of bacterial cell division. Structurally, FtsZ is a homolog of eukaryotic tubulin but has low sequence similarity; this makes it possible to obtain FtsZ inhibitors without affecting the eukaryotic cell division. Computational studies were performed on a series of substituted 3-arylalkoxybenzamide derivatives reported as inhibitors of FtsZ activity in Staphylococcus aureus. Quantitative structure-activity relationship models (QSAR) models generated showed good statistical reliability, which is evident from r2ncv and r2loo values. The predictive ability of these models was determined and an acceptable predictive correlation (r2Pred) values were obtained. Finally, we performed molecular dynamics simulations in order to examine the stability of protein-ligand interactions. This facilitated us to compare free binding energies of cocrystal ligand and newly designed molecule B1. The good concordance between the docking results and comparative molecular field analysis (CoMFA)/comparative molecular similarity indices analysis (CoMSIA) contour maps afforded obliging clues for the rational modification of molecules to design more potent FtsZ inhibitors.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Ballu S
a Department of Chemistry , University College of Science, Osmania University , Hyderabad , India.
Itteboina R
a Department of Chemistry , University College of Science, Osmania University , Hyderabad , India.
Sivan SK
a Department of Chemistry , University College of Science, Osmania University , Hyderabad , India.
Manga V
a Department of Chemistry , University College of Science, Osmania University , Hyderabad , India.

MeSH

Bacterial ProteinsCytoskeletal ProteinsDrug DesignHumansLigandsMolecular Docking SimulationMolecular Dynamics SimulationQuantitative Structure-Activity RelationshipStaphylococcal InfectionsStaphylococcus aureus

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29369011

Citation

Ballu, Srilata, et al. "Structural Insights of Staphylococcus Aureus FtsZ Inhibitors Through Molecular Docking, 3D-QSAR and Molecular Dynamics Simulations." Journal of Receptor and Signal Transduction Research, vol. 38, no. 1, 2018, pp. 61-70.
Ballu S, Itteboina R, Sivan SK, et al. Structural insights of Staphylococcus aureus FtsZ inhibitors through molecular docking, 3D-QSAR and molecular dynamics simulations. J Recept Signal Transduct Res. 2018;38(1):61-70.
Ballu, S., Itteboina, R., Sivan, S. K., & Manga, V. (2018). Structural insights of Staphylococcus aureus FtsZ inhibitors through molecular docking, 3D-QSAR and molecular dynamics simulations. Journal of Receptor and Signal Transduction Research, 38(1), 61-70. https://doi.org/10.1080/10799893.2018.1426607
Ballu S, et al. Structural Insights of Staphylococcus Aureus FtsZ Inhibitors Through Molecular Docking, 3D-QSAR and Molecular Dynamics Simulations. J Recept Signal Transduct Res. 2018;38(1):61-70. PubMed PMID: 29369011.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structural insights of Staphylococcus aureus FtsZ inhibitors through molecular docking, 3D-QSAR and molecular dynamics simulations. AU - Ballu,Srilata, AU - Itteboina,Ramesh, AU - Sivan,Sree Kanth, AU - Manga,Vijjulatha, PY - 2018/1/26/entrez PY - 2018/1/26/pubmed PY - 2018/8/14/medline KW - CoMFA KW - CoMSIA KW - FtsZ KW - MD KW - PLS KW - XP SP - 61 EP - 70 JF - Journal of receptor and signal transduction research JO - J Recept Signal Transduct Res VL - 38 IS - 1 N2 - Filamentous temperature-sensitive protein Z (FtsZ) is a protein encoded by the FtsZ gene that assembles into a Z-ring at the future site of the septum of bacterial cell division. Structurally, FtsZ is a homolog of eukaryotic tubulin but has low sequence similarity; this makes it possible to obtain FtsZ inhibitors without affecting the eukaryotic cell division. Computational studies were performed on a series of substituted 3-arylalkoxybenzamide derivatives reported as inhibitors of FtsZ activity in Staphylococcus aureus. Quantitative structure-activity relationship models (QSAR) models generated showed good statistical reliability, which is evident from r2ncv and r2loo values. The predictive ability of these models was determined and an acceptable predictive correlation (r2Pred) values were obtained. Finally, we performed molecular dynamics simulations in order to examine the stability of protein-ligand interactions. This facilitated us to compare free binding energies of cocrystal ligand and newly designed molecule B1. The good concordance between the docking results and comparative molecular field analysis (CoMFA)/comparative molecular similarity indices analysis (CoMSIA) contour maps afforded obliging clues for the rational modification of molecules to design more potent FtsZ inhibitors. SN - 1532-4281 UR - https://www.unboundmedicine.com/medline/citation/29369011/Structural_insights_of_Staphylococcus_aureus_FtsZ_inhibitors_through_molecular_docking_3D_QSAR_and_molecular_dynamics_simulations_ DB - PRIME DP - Unbound Medicine ER -