title: In silico binding analysis of Withanolides with the Human GM-CSFR.
abstract: Experimental studies have shown that Withanolides are group of pharmacologically active compounds (steroidal lactones), immunomodulatory agents mainly present in the leaves and roots of Withania somnifera plant. The present study is about virtual screening of Withanolide compounds to check for drug likeness by Lipinski's rule five and the screened compounds are allowed to binding with the human GM-CSFR, an immunomodulatory cytokine receptor expressed on dendritic cells. The binding pocket sites, the internal energy, the hydrogen bond interactions and the interacting amino acid residues of the human GM-CSFR with Withanolides were analyzed through molecular docking method. Among the Withanolides docked with human GM-CSFR, which is responsible for DCs survival, proliferation and differentiation, Withanolide A was identified to be a lead compound by binding with α subunit of GM-CSFR exhibiting a maximum Dock score of 28.07 and internal binding energy of -12.8 Kcal/mol. Levamisole as a standard immunomodulatory agent has shown maximum dock score of 28.639 and internal binding energy of -1.864 Kcal/mol. Withanolide A and Levamisole was docked with similar binding site amino acid, ARG302 of GM-CSFR. In addition, Withanolide A was also binding with LEU246 of GM-CSFR, as binding aminoacids predicted from PDBSUM.
authors.affiliation: Department of Biotechnology, Sri Venkateswara College of Engineering, Sriperumbudur, Tamilnadu, India.
authors.forename: Posa Krishnamoorthy
authors.initials: PK
authors.lastname: Praveen Kumar
authors.affiliation: Department of Biotechnology, Sri Venkateswara College of Engineering, Sriperumbudur, Tamilnadu, India.
authors.forename: Muthukumaran
authors.initials: M
authors.lastname: Sivanandham
authors.affiliation: Department of Biotechnology, Sri Venkateswara College of Engineering, Sriperumbudur, Tamilnadu, India.
authors.forename: Lavanya
authors.initials: L
authors.lastname: Damodharan
mesh_terms: D001665:Binding Sites; D006801:Humans; D062105:Molecular Docking Simulation; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry*; D054358:Withanolides / Q000737:chemistry*
chemical_list: D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D054358:Withanolides