Examining the Structural Differences in Different Cannibinoids and How They Interact with Receptors in the Brain

Yashvi Patel

Abstract

There are both natural cannabinoids (Delta-8 and Delta-9 THC) that bind to the cannabinoid CB1 and CB2 receptors, as well as synthetic cannabinoids (WIN55-212,2, JWH-018, and Provadoline). How these molecules affect the brain depends on which receptor they bind to more strongly: CB1 has more psychoactive effects, whereas CB2 has more medicinal effects. The goal of this study was to examine the structure and binding energy of each cannabinoid upon binding to each receptor. The differences in structure between the molecules was analyzed to understand differences in binding. This was done using AutoDock Vina, a computational docking software where the ligand (cannabinoid) simulates binding to the macromolecule (receptor) and records the binding site and affinities. Through the fixed docking methodology, I obtained results that contradicted experimentally determined data about how well the cannabinoids bind to each of the receptors. Flexible docking was then performed, in which the receptors adapt flexibly to the ligands, but this further contradicted background information. The synthetic cannabinoids should be stronger binders to the CB1 receptor, but docking showed the ligands bound more strongly to the CB2 receptor. I hypothesized that the CB2 receptor file from the PDB was biased to have a more open binding site than CB1 structure from the PDB. Looking at the Poseview images from some of the stronger binding ligands, I was able to identify what characteristics in the structures of each of the compounds led to the changes in strength of binding between each receptor. and the ligand.

 
Apr 2nd, 11:00 AM

Examining the Structural Differences in Different Cannibinoids and How They Interact with Receptors in the Brain

HSS 202

There are both natural cannabinoids (Delta-8 and Delta-9 THC) that bind to the cannabinoid CB1 and CB2 receptors, as well as synthetic cannabinoids (WIN55-212,2, JWH-018, and Provadoline). How these molecules affect the brain depends on which receptor they bind to more strongly: CB1 has more psychoactive effects, whereas CB2 has more medicinal effects. The goal of this study was to examine the structure and binding energy of each cannabinoid upon binding to each receptor. The differences in structure between the molecules was analyzed to understand differences in binding. This was done using AutoDock Vina, a computational docking software where the ligand (cannabinoid) simulates binding to the macromolecule (receptor) and records the binding site and affinities. Through the fixed docking methodology, I obtained results that contradicted experimentally determined data about how well the cannabinoids bind to each of the receptors. Flexible docking was then performed, in which the receptors adapt flexibly to the ligands, but this further contradicted background information. The synthetic cannabinoids should be stronger binders to the CB1 receptor, but docking showed the ligands bound more strongly to the CB2 receptor. I hypothesized that the CB2 receptor file from the PDB was biased to have a more open binding site than CB1 structure from the PDB. Looking at the Poseview images from some of the stronger binding ligands, I was able to identify what characteristics in the structures of each of the compounds led to the changes in strength of binding between each receptor. and the ligand.