Poster Presentation ANZOS Annual Scientific Meeting 2021

Mechanisms of Action of Cassiae Semen for Weight Management: A Computational Molecular Docking Study of Serotonin Receptor 5-HT2C (#248)

Heidi Yuen 1 , George Lenon 1 , Andrew Hung 2 , Angela Yang 1
  1. School of Health and Biomedical sciences, RMIT University, bundoora, Vic, Australia
  2. School of Science, RMIT University, Melbourne, Vic, Australia

Background: The epidemic of obesity has become a major challenge to health globally with overeating as one of the major casual factors. The serotonin receptor, 5-HT2C, is known to mediate satiety, appetite and consumption behaviour. Anti-obesity drug lorcaserin has demonstrated efficacy targeting 5-HT2C but can cause undesirable side effects. Cassiae Semen (CS), a well-known traditional Chinese herbal medicine for weight management, promotes satiety in recommended dosage without any side effects.  

Aim: To evaluate the interactions of 5-HT2C receptor to the CS ligands, and hence, to propose the CS compounds responsible for exerting anti-obesity effects via appetite suppression.

Methods: A computational molecular docking study was performed to determine the binding mechanism of CS compounds to 5-HT2C in both conformations of active agonist-bound (chain A of PDBID: 6BQG) and inactive antagonist-bound (chain A of PDBID: 6BQH). The molecular docking software used in this study was AutoDock Vina version 1.1.2 [1] while the binding site and ligand interaction analysis and 2D protein-ligand interaction diagram generation were performed with software Maestro [2] from Schrodinger.

Results: By comparing binding poses and predicted relative binding affinities towards the active or inactive forms of the receptor, we hypothesise that two of the CS compounds studied may be potent agonists mimicing the appetite suppression effects of lorcaserin: obtusifoliol and cassiaside B2. Furthermore, two ligands, beta-sitosterol and juglanin, were predicted to bind favourably to 5-HT2C outside of the known agonist binding pocket in the active receptor, suggesting that such ligands may serve as positive allosteric modulators of 5-HT2C receptor function. Findings of this study have been published [3].


  1. Trott, O. and A.J. Olson, AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 2010. 31(2): p. 455-461.
  2. Schrodinger. Maestro - The completely reimagined all-purpose molecular modeling environment. 2020 20 Jan 2020].
  3. Yuen, H., et al., Mechanisms of Action of Cassiae Semen for Weight Management: A Computational Molecular Docking Study of Serotonin Receptor 5-HT2C. Int J Mol Sci, 2020. 21(4): p. 1326.