Decoding the Molecular Dance: In Silico Exploration of Cannabinoid Interactions with Key Protein Targets for Therapeutic Insights

Abstract

As hemp-based cannabinoids are continuously gaining popularity, synthesis and extraction methods for these compounds are ever-changing. Within the cannabinoid market, hydrogenated derivatives are also gaining popularity at an accelerated rate, with the need for in-depth analysis of these compounds pertinent to increasing the knowledge of cannabis chemistry. Our lab used Schrödinger to dock natural and synthetic cannabinoids in various CB1 and CB2 receptors, PPAR-γ, PAK1, and GPR119 complex including several enzymes, to evaluate the interacting residues within the known binding pockets, comprising the computation of binding energies, predicting ADME characteristics, and evaluating P450 sites of metabolism. The purpose of identifying active residues, sites of metabolism, and ADME characteristics for 40 various cannabinoids is to provide guidance in computer-aided drug design and rationalization in designing and synthesis of analogs.