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. 2022 Jul 22;12(1):12547.
doi: 10.1038/s41598-022-16102-9.

Molecular docking analysis and evaluation of the antimicrobial properties of the constituents of Geranium wallichianum D. Don ex Sweet from Kashmir Himalaya

Affiliations

Molecular docking analysis and evaluation of the antimicrobial properties of the constituents of Geranium wallichianum D. Don ex Sweet from Kashmir Himalaya

Wajahat Rashid Mir et al. Sci Rep. .

Abstract

Geranium wallichianum D. Don ex Sweet is a well-known medicinal plant in Kashmir Himalya. The evidence for its modern medicinal applications remains majorly unexplored. The present study was undertaken to elucidate the detailed antimicrobial promises of different crude extracts (methanolic, ethanolic, petroleum ether, and ethyl acetate) of G. wallichainum against common human bacterial and fungal pathogens in order to scientifically validate its traditional use. The LC-MS analysis of G. wallichainum yielded 141 bioactive compounds with the vast majority of them having therapeutic applications. Determination of minimum inhibitory concentrations (MICs) by broth microdilution method of G. wallichainum was tested against bacterial and fungal pathogens with MICs ranging from 0.39 to 400 µg/mL. Furthermore, virtual ligands screening yielded elatine, kaempferol, and germacrene-A as medicinally most active constituents and the potential inhibitors of penicillin-binding protein (PBP), dihydropteroate synthase (DHPS), elongation factor-Tu (Eu-Tu), ABC transporter, 1,3 beta glycan, and beta-tubulin. The root mean square deviation (RMSD) graphs obtained through the molecular dynamic simulations (MDS) indicated the true bonding interactions which were further validated using root mean square fluctuation (RMSF) graphs which provided a better understanding of the amino acids present in the proteins responsible for the molecular motions and fluctuations. The effective binding of elatine, kaempferol, and germacrene-A with these proteins provides ground for further research to understand the underlying mechanism that ceases the growth of these microbes.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
3D structure of different microbial target proteins.
Figure 2
Figure 2
LC–MS-ESI–MS chromatograms of reference compounds using Nexera in Methanolic extract.
Figure 3
Figure 3
Structures of the compounds identified based on LC–MS from G. wallichainum.
Figure 4
Figure 4
(a) 3D interactions of Ligands with (A) Dihydropteroate synthase (B) Elongation factor Tu and (C) Penicillin Binding Protein (D) ABC transporter (E) 1,3-Betaglycan (F) Beta-tubulin with Elatine and 2D structure of ligands interacted with respective amino acids. Read the text for further information. (b) 3D interactions of Ligands with (A) Dihydropteroate synthase (B) Elongation factor Tu and (C) Penicillin Binding Protein (D) ABC transporter (E) 1,3-Betaglycan (F) Beta-tubulin with Kaempherol and 2D structure of ligands interacted with respective amino acids. Read the text for further information. (c). 3D interactions of Ligands with (A) Dihydropteroate synthase (B) Elongation factor Tu and (C) Penicillin Binding Protein (D) ABC transporter (E) 1,3-Betaglycan (F) Beta-tubulin with Germacrene A and 2D structure of ligands interacted with respective amino acids. Read the text for further information.
Figure 4
Figure 4
(a) 3D interactions of Ligands with (A) Dihydropteroate synthase (B) Elongation factor Tu and (C) Penicillin Binding Protein (D) ABC transporter (E) 1,3-Betaglycan (F) Beta-tubulin with Elatine and 2D structure of ligands interacted with respective amino acids. Read the text for further information. (b) 3D interactions of Ligands with (A) Dihydropteroate synthase (B) Elongation factor Tu and (C) Penicillin Binding Protein (D) ABC transporter (E) 1,3-Betaglycan (F) Beta-tubulin with Kaempherol and 2D structure of ligands interacted with respective amino acids. Read the text for further information. (c). 3D interactions of Ligands with (A) Dihydropteroate synthase (B) Elongation factor Tu and (C) Penicillin Binding Protein (D) ABC transporter (E) 1,3-Betaglycan (F) Beta-tubulin with Germacrene A and 2D structure of ligands interacted with respective amino acids. Read the text for further information.
Figure 4
Figure 4
(a) 3D interactions of Ligands with (A) Dihydropteroate synthase (B) Elongation factor Tu and (C) Penicillin Binding Protein (D) ABC transporter (E) 1,3-Betaglycan (F) Beta-tubulin with Elatine and 2D structure of ligands interacted with respective amino acids. Read the text for further information. (b) 3D interactions of Ligands with (A) Dihydropteroate synthase (B) Elongation factor Tu and (C) Penicillin Binding Protein (D) ABC transporter (E) 1,3-Betaglycan (F) Beta-tubulin with Kaempherol and 2D structure of ligands interacted with respective amino acids. Read the text for further information. (c). 3D interactions of Ligands with (A) Dihydropteroate synthase (B) Elongation factor Tu and (C) Penicillin Binding Protein (D) ABC transporter (E) 1,3-Betaglycan (F) Beta-tubulin with Germacrene A and 2D structure of ligands interacted with respective amino acids. Read the text for further information.
Figure 5
Figure 5
Protein–ligand RMSD plot.
Figure 6
Figure 6
Protein–RMSF plot.
Figure 7
Figure 7
Hydrogen bond contact analysis of lead compound and elatine–protein complexes. Various intermolecular interactions made by elatine–protein amino acid residues with lead ligand during molecular dynamics simulations. Bar colors: Hydrogen bond (Green), Hydrophobic (Purple), Water bridge (Blue).
Figure 8
Figure 8
A schematic of detailed ligand atom interactions with the protein residues. Interactions that occur more than 30.0% of the simulation time in the selected trajectory (0.00 through 100.00 nsec), are shown.

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