Exploring In silico Properties of Human 5-HT3 Receptor As A Potential Target For Smoking Cessation

Event Abstract Back to Event Exploring In silico> Properties of Human 5-HT3 Receptor As A Potential Target For Smoking Cessation Muhammad Harith Zulkifli1, Lam Kok Wai1, Shuhaila Mat Shaarani2, Malina Jasamai1 and Nor Syafinaz Yaakob1* 1 Drug and Herbal Research Centre, Faculty of Pharmacy, University Kebangsaan Malaysia, Malaysia 2 Malaysia Genome Institute, Malaysia Background The serotonin or 5-hydroxytryptamine subtype 3 receptor (5-HT3R) is a potential target for the treatment of drug addiction. This study explores possibility of using the 5-HT3R antagonists for the treatment of nicotine abuse by understanding it at the molecular level. However, the structure of human 5-HT3R is not yet fully understood, therefore this study first aimed to construct an in silico functional model of 5-HT3R to have a deeper understanding on the receptor binding and activation/inhibition with ligands such as nicotine and 5-HT3R antagonists like palonosetron and the natural bioactive compound gingerol. Methods Homology model of human 5-HT3A receptor was constructed using Swiss Model approach. The model was submitted for scoring by Ramachandran Plot, Verify3D, ERRAT and ProSA. Following preorientation with respect to the lipid bilayer, serotonin docking and addition of charges, lipid bilayer, water molecules and ions forming a system, it was sent for molecular dynamic (MD) simulation using Gromacs 2016. For docking studies, nicotine, palonosetron and 6-gingerol were docked individually into the orthosteric binding site using AutoDock Vina. Results Scores of the model were 86.2% (Ramachandran Plot), 45.39% (Verify3D), 93.38 (ERRAT) and -5.51 (ProSA), indicating that the model was good for MD simulation. Docking studies showed that cation-π interaction between nicotine and tryptophan group, multiple aromatic and hydrophobic interactions at tricyclic ring of palonosetron, and interactions of 6-gingerol with R87 and N123 residues were respectively observed similar to other conducted studies. Conclusion Construction of an in silico functional model of 5-HT3R is useful in order to understand the interactions between the receptor and various ligands. The model allows elucidation of nicotine action on 5-HT3R as an antagonist, which can possibly be competed with other 5-HT3R antagonists such as palonosetron and gingerol. This positioned the 5-HT3R as a good potential target for smoking cessation strategies either as an alternative or adjunct treatment. Keywords: Serotonin, 5-HT3 receptor, Nicotine, Gingerol, Palonosetron Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Poster Presentation Topic: Miscellaneous Citation: Zulkifli M, Kok Wai L, Mat Shaarani S, Jasamai M and Yaakob N (2019). Exploring In silico> Properties of Human 5-HT3 Receptor As A Potential Target For Smoking Cessation. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2019.63.00033 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Sep 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Nor Syafinaz Yaakob, Drug and Herbal Research Centre, Faculty of Pharmacy, University Kebangsaan Malaysia, Kuala Lampur, 50300, Malaysia, nsy@ukm.edu.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Muhammad Harith Zulkifli Lam Kok Wai Shuhaila Mat Shaarani Malina Jasamai Nor Syafinaz Yaakob Google Muhammad Harith Zulkifli Lam Kok Wai Shuhaila Mat Shaarani Malina Jasamai Nor Syafinaz Yaakob Google Scholar Muhammad Harith Zulkifli Lam Kok Wai Shuhaila Mat Shaarani Malina Jasamai Nor Syafinaz Yaakob PubMed Muhammad Harith Zulkifli Lam Kok Wai Shuhaila Mat Shaarani Malina Jasamai Nor Syafinaz Yaakob Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.