KAJIAN INTERAKSI SENYAWA TURUNAN CANNABINOID TERHADAP RESEPTOR CB1 SECARA IN SILICO

• Main Author: Evania Wijaya, Felicia
• Format: Final Project
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/56692
• Institution: Institut Teknologi Bandung

Cannabinoid is a class of compounds with the potential to produce therapeutic effects through its interaction with cannabinoid receptor type 1 and/or 2. ? 9 -tetrahydrocannabinol is one of the cannabinoids that has been medically used to treat Acquired Immunodeficiency Syndrome (AIDS) patients who experience drastic weight loss, and post-chemotherapy patients who experience nausea and vomiting but cannot be treated with conventional antiemetics. However, the use of cannabinoids in Indonesia is still limited by the legality aspect. This study aimed to examine the interaction of cannabinoid derivatives with unknown activity against the cannabinoid receptor type 1 (CB1 receptor). The three-dimensional structure of CB1 receptor was obtained from the RCSB Protein Data Bank (PDB ID 6N4B). Ligand preparation was performed by geometry optimization of the cannabinoid derivatives using Gaussian09 software. The geometry optimization method used is Density Functional Theory Restricted B3LYP with 6-31 G basis set. Furthermore, interaction studies were carried out through docking simulation using AutoDock 4.2.6 software and MGL Tools 1.5.6, as well as molecular dynamics simulation for 100 ns using Amber16 software. The simulation results were analyzed using UCSF Chimera 1.14 software and BIOVIA Discovery Studio Visualizer 2021. The calculation of the free energy value was carried out using the Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) method. Based on the study interaction of ligand with CB1 receptor, it was found that the compound number 18, 17, 19, 6, 7, and 5 could bind in the same position as reference compounds binding site. The free binding energy of compound 18, 17, and 19 against the CB1 receptor were ?145.62747 kJ/mol, ?142.82461 kJ/mol, and ?142.33215 kJ/mol, respectively. Furthermore, compounds 18, 17, and 19 are proposed to be further tested by in vitro and in vivo approach.