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

The study focuses on M1069, a promising drug for solid tumors functioning as an A2A adenosine receptor antagonist. Herein, we investigate the binding mechanism of the drug molecule M1069 by employing computational techniques to draw comparisons with Human serum albumin (HSA), shedding light on the intricate interactions between M1069 and its target as well. The molecular docking results suggest that the drug molecule binds very well with the HSA protein when compared to A2AAR with the docking score of −7.02 kcal/mol. To substantiate the molecular interactions between the drug and the protein structure, comprehensive molecular dynamic simulations were performed for a period of 100 ns. This approach facilitated an in-depth analysis of the dynamic relationships and behaviors between the drug and the protein, offering valuable insights into their intermolecular dynamics and stability. Subsequently, DFT analysis is conducted to assess the inhibitory efficacy of the drug, employing the B3LYP technique. Additionally, an investigation into the pharmacological ADMET parameters of the drug molecule resulted in gastrointestinal absorption. These outcomes contribute to a better understanding of the interaction dynamics between the drug and the proteins, providing valuable insights that can enhance the drug discovery process.