Virtual Winter School on Computational Chemistry
M.Sc. Moola Nyambe
Department of Physics, Chemistry and Material Science, University of Namibia (UNAM)
Xerantholide is a sesquiterpene lactone that is commonly found in plants, and it exhibits anti-gonorrhea activity. Using molecular docking, the possible mode of action of xerantholide against Neisseria gonorrhoeae was studied, namely its interaction with N. gonorrhoeae carbonic anhydrase (NgCA). The results show that xerantholide interacts with the active site of NgCA via hydrogen bonding, metal-acceptor interaction, and non-polar alkyl and pi-alkyl interactions. The predicted binding affinity of -6.8 kcal/mol compares well with that obtained for standard NgCA inhibitor like acetazolamide (-5.7 kcal/mol). A biomimetic model study involving xerantholide and zinc-tris imidazole ([ZnIm3]2+) ion was also carried out at different theoretical levels to estimate the interaction energy for the formation of the complex between the ligand and the NgCA active site model. The binding free energy (ΔG) was calculated to be -28.5 kcal/mol at the B3LYP/6-311++G(d,p) level. The interaction mode observed in both the docking and the model calculations involves the lactone ring.
Xerantholide-NgCA complex
References
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