Insight into the Binding Interaction Mechanism of the ligand M1069 with Human Serum Albumin and A2A Adenosine Receptor – A Biophysical Approach

Adenosine, a nucleotide essential for human energy metabolism, can also increase the development and metastasis of cancer. Through its interaction to G protein-coupled adenosine receptors (GPCRs), adenosine can stimulate the growth and proliferation of cancer cells. Recent research suggests that drug M1069, which is developed as a treatment for alpha-1 antitrypsin deficiency (AATD), a hereditary condition that can cause lung and liver damage, can also be useful in cancer treatment as an antagonist. It prevents adenosine from binding to the protein A2A adenosine receptor on G-coupled receptors. This study examines the fundamentals of the drug M1069 and its interactions with the A2AAR (target) and HSA (transport) proteins. In this investigation, we are endeavoring to determine the electronic characteristics of the M1069 when it interacts with the HSA and A2AAR protein. Molecular Docking simulation is carried out in order to gain an understanding of the mechanism underlying the binding interaction. Molecular dynamics simulations were applied to the optimal docked pose determined from docking investigations. In addition, the optimization of the ligand and single point energy calculations were performed using density functional theory (DFT) before and after docking to gain insight into the intermolecular interaction and investigate the electronic characteristics of the docked molecules.