Molecular docking studies of natural immunomodulators indicate their interactions with the CD40L of CD40/CD40L pathway and CSF1R kinase domain of microglia

J Mol Model. 2022 Mar 24;28(4):101. doi: 10.1007/s00894-022-05084-0.

Abstract

Natural products have proved beneficial in reducing neuroinflammation in neurological diseases. Their impacts have also been associated with the activities of microglia, responsible for brain-specific immunity. Recent studies have shown the involvement of the number of microglia-specific proteins in the regulation of brain-specific immunity. However, molecular targets of natural products and their mechanism of interaction with microglia-specific proteins are elusive. Since the genetic signature of microglia offers many potential targets for drug discovery, molecular docking followed by molecular dynamics (MD) simulations of cluster of differentiation 40 ligand (CD40L) and colony-stimulating factor 1 receptor (CSF1R) kinase domain protein with some known neuro-immunomodulators (Curcumin, Cannabidiol, Ginsenoside Rg1, Resveratrol, and Sulforaphane) has been evaluated. Curcumin and cannabidiol were observed likely to modulate CD40L and expression of cytokines and entry of inflammatory cells. Resveratrol and cannabidiol may affect the CSF1R kinase domain and activation of microglia. Our finding suggests that curcumin, cannabidiol, and resveratrol may serve specific drug ligands in regulating microglia-mediated brain immunity.

Keywords: Drug target; MD simulation; Microglia; Molecular docking; Natural products; Protein–ligand interaction.

MeSH terms

  • CD40 Ligand* / metabolism
  • Immunologic Factors / metabolism
  • Ligands
  • Microglia* / metabolism
  • Molecular Docking Simulation

Substances

  • Immunologic Factors
  • Ligands
  • CD40 Ligand