Predictive binding affinity of plant-derived natural products towards the protein kinase G enzyme of Mycobacterium tuberculosis (MtPknG)

Rana M. Qasaymeh, Dino Rotondo, Carel B. Oosthuizen, Namrita Lall, Veronique Seidel

Research output: Contribution to journalArticle

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a growing public health concern worldwide, especially with the emerging challenge of drug resistance to the current drugs. Efforts to discover and develop some novel, more effective and safer anti-TB drugs are urgently needed. Products from natural sources, such as medicinal plants, have long played an important role in traditional medicine and continue to provide some inspiring templates for the design of new drugs. Protein kinase G, produced by M. tuberculosis (MtPKnG), is a serine/threonine kinase that has been reported to prevent phagosome-lysosome fusion and help prolong M. tuberculosis survival within the host’s macrophages. Here, we used an in silico target-based approach (docking) to predict the interactions between MtPknG and 84 chemical constituents from two medicinal plants (Pelargonium reniforme and Pelargonium sidoides) that have a well-documented historical use as natural remedies for TB. Docking scores for ligands towards the target protein were calculated using AutoDock Vina as the predicted binding free energies. Ten flavonoids present in the aerial parts of P. reniforme and/or P. sidoides showed docking scores ranging from -11.1 to -13.2 kcal/mol. Upon calculation of all ligand efficiency indices, we observed that the (- G/MW) ligand efficiency index for flavonoids (4), (5) and (7) was similar to the one obtained for the AX20017 control. When taking all compounds into account, we observed that the best (- G/MW) efficiency index was obtained for coumaric acid, coumaraldehyde, p-hydroxyphenyl acetic acid and p-hydroxybenzyl alcohol. We found that methyl gallate and myricetin had ligand efficiency indices superior and equal to the AX20017 control efficiency, respectively. It remains to be seen if any of the compounds screened in this study exert an effect in M. tuberculosis-infected macrophages.
LanguageEnglish
Article number477
Number of pages14
JournalPlants
Volume8
Issue number11
DOIs
Publication statusPublished - 6 Nov 2019

Fingerprint

Biological Products
Pelargonium
Mycobacterium tuberculosis
Ligands
Tuberculosis
Enzymes
Medicinal Plants
Flavonoids
Macrophages
Phagosomes
Drug Design
Protein-Serine-Threonine Kinases
Traditional Medicine
Lysosomes
Drug Resistance
Acetic Acid
Pharmaceutical Preparations
Computer Simulation
Public Health
Mycobacterium tuberculosis protein kinase G

Keywords

  • AutoDock Vina
  • flavonoids
  • molecular docking
  • Mycobacterium tuberculosis
  • Pelargonium reniforme
  • Pelargonium sidoides
  • protein kinase G (PknG)
  • SiteMap

Cite this

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title = "Predictive binding affinity of plant-derived natural products towards the protein kinase G enzyme of Mycobacterium tuberculosis (MtPknG)",
abstract = "Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a growing public health concern worldwide, especially with the emerging challenge of drug resistance to the current drugs. Efforts to discover and develop some novel, more effective and safer anti-TB drugs are urgently needed. Products from natural sources, such as medicinal plants, have long played an important role in traditional medicine and continue to provide some inspiring templates for the design of new drugs. Protein kinase G, produced by M. tuberculosis (MtPKnG), is a serine/threonine kinase that has been reported to prevent phagosome-lysosome fusion and help prolong M. tuberculosis survival within the host’s macrophages. Here, we used an in silico target-based approach (docking) to predict the interactions between MtPknG and 84 chemical constituents from two medicinal plants (Pelargonium reniforme and Pelargonium sidoides) that have a well-documented historical use as natural remedies for TB. Docking scores for ligands towards the target protein were calculated using AutoDock Vina as the predicted binding free energies. Ten flavonoids present in the aerial parts of P. reniforme and/or P. sidoides showed docking scores ranging from -11.1 to -13.2 kcal/mol. Upon calculation of all ligand efficiency indices, we observed that the (- G/MW) ligand efficiency index for flavonoids (4), (5) and (7) was similar to the one obtained for the AX20017 control. When taking all compounds into account, we observed that the best (- G/MW) efficiency index was obtained for coumaric acid, coumaraldehyde, p-hydroxyphenyl acetic acid and p-hydroxybenzyl alcohol. We found that methyl gallate and myricetin had ligand efficiency indices superior and equal to the AX20017 control efficiency, respectively. It remains to be seen if any of the compounds screened in this study exert an effect in M. tuberculosis-infected macrophages.",
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Predictive binding affinity of plant-derived natural products towards the protein kinase G enzyme of Mycobacterium tuberculosis (MtPknG). / M. Qasaymeh, Rana; Rotondo, Dino; Oosthuizen, Carel B.; Lall, Namrita; Seidel, Veronique.

Vol. 8, No. 11, 477, 06.11.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Predictive binding affinity of plant-derived natural products towards the protein kinase G enzyme of Mycobacterium tuberculosis (MtPknG)

AU - M. Qasaymeh, Rana

AU - Rotondo, Dino

AU - Oosthuizen, Carel B.

AU - Lall, Namrita

AU - Seidel, Veronique

PY - 2019/11/6

Y1 - 2019/11/6

N2 - Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a growing public health concern worldwide, especially with the emerging challenge of drug resistance to the current drugs. Efforts to discover and develop some novel, more effective and safer anti-TB drugs are urgently needed. Products from natural sources, such as medicinal plants, have long played an important role in traditional medicine and continue to provide some inspiring templates for the design of new drugs. Protein kinase G, produced by M. tuberculosis (MtPKnG), is a serine/threonine kinase that has been reported to prevent phagosome-lysosome fusion and help prolong M. tuberculosis survival within the host’s macrophages. Here, we used an in silico target-based approach (docking) to predict the interactions between MtPknG and 84 chemical constituents from two medicinal plants (Pelargonium reniforme and Pelargonium sidoides) that have a well-documented historical use as natural remedies for TB. Docking scores for ligands towards the target protein were calculated using AutoDock Vina as the predicted binding free energies. Ten flavonoids present in the aerial parts of P. reniforme and/or P. sidoides showed docking scores ranging from -11.1 to -13.2 kcal/mol. Upon calculation of all ligand efficiency indices, we observed that the (- G/MW) ligand efficiency index for flavonoids (4), (5) and (7) was similar to the one obtained for the AX20017 control. When taking all compounds into account, we observed that the best (- G/MW) efficiency index was obtained for coumaric acid, coumaraldehyde, p-hydroxyphenyl acetic acid and p-hydroxybenzyl alcohol. We found that methyl gallate and myricetin had ligand efficiency indices superior and equal to the AX20017 control efficiency, respectively. It remains to be seen if any of the compounds screened in this study exert an effect in M. tuberculosis-infected macrophages.

AB - Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a growing public health concern worldwide, especially with the emerging challenge of drug resistance to the current drugs. Efforts to discover and develop some novel, more effective and safer anti-TB drugs are urgently needed. Products from natural sources, such as medicinal plants, have long played an important role in traditional medicine and continue to provide some inspiring templates for the design of new drugs. Protein kinase G, produced by M. tuberculosis (MtPKnG), is a serine/threonine kinase that has been reported to prevent phagosome-lysosome fusion and help prolong M. tuberculosis survival within the host’s macrophages. Here, we used an in silico target-based approach (docking) to predict the interactions between MtPknG and 84 chemical constituents from two medicinal plants (Pelargonium reniforme and Pelargonium sidoides) that have a well-documented historical use as natural remedies for TB. Docking scores for ligands towards the target protein were calculated using AutoDock Vina as the predicted binding free energies. Ten flavonoids present in the aerial parts of P. reniforme and/or P. sidoides showed docking scores ranging from -11.1 to -13.2 kcal/mol. Upon calculation of all ligand efficiency indices, we observed that the (- G/MW) ligand efficiency index for flavonoids (4), (5) and (7) was similar to the one obtained for the AX20017 control. When taking all compounds into account, we observed that the best (- G/MW) efficiency index was obtained for coumaric acid, coumaraldehyde, p-hydroxyphenyl acetic acid and p-hydroxybenzyl alcohol. We found that methyl gallate and myricetin had ligand efficiency indices superior and equal to the AX20017 control efficiency, respectively. It remains to be seen if any of the compounds screened in this study exert an effect in M. tuberculosis-infected macrophages.

KW - AutoDock Vina

KW - flavonoids

KW - molecular docking

KW - Mycobacterium tuberculosis

KW - Pelargonium reniforme

KW - Pelargonium sidoides

KW - protein kinase G (PknG)

KW - SiteMap

UR - https://www.mdpi.com/journal/plants

U2 - 10.3390/plants8110477

DO - 10.3390/plants8110477

M3 - Article

VL - 8

IS - 11

M1 - 477

ER -