O receptor Canabinoide 1 : desafios no desenho de fármacos com enfoque nas ferramentas da bioinformática

Abstract

Cannabinoid Receptor 1 (CB1) is a membrane protein prevalent in the Central Nervous System (SNC), whose crystallographic structure has recently been solved. Studies will be needed to investigate CB1 complexes with its ligands and its role in the development of new drugs. Our goal here was to carry out computational simulations of CB1, with focus on its interations with potential ligands. We start with a literature review, and then we describe recent studies on CB1 crystallographic structure. We report the development of a docking protocol to investigate potential ligands against CB1. We use this structural information to depict CB1-ligand interactions. We also describe the molecular docking method to obtain complex structures of CB1 with inverse agonists, and also with agonists. Analisis of the crystallographic structure and docking results revealed the residues responsible for the specificity of the inverse agonists and agonists for CB1. Most of the intermolecular interactions involve hydrophobic residues, and some intermolecular hydrogen bonds highlighting the importance of the exploration of intermolecular interactions in the development of novel inverse agonists.