P2Y12 Human Receptor Complexed With AZD1283, Cholesterol, and Monoolein Raman Spectra DFT Simulation

ABSTRACT The paper reports the results of a theoretical Raman spectroscopy simulation for the human platelet P2Y12 receptor complex with the antagonists AZD1283, cholesterol, and monoolein. The obtained data demonstrate the predominance of vibrational modes associated with ligand stability due to amino acid residues, indicating a lack of significant conformational changes in the receptor's secondary structure. RDG analysis confirms the dominance of van der Waals forces for all ligands, with no significant contribution from hydrogen bonds, despite the results obtained from molecular docking simulations. The simulation results suggest that ligands are sterically incorporated into the lipid‐protein matrix of the P2Y12 receptor through dominant van der Waals interactions, indicating potential for the development of a novel generation of P2Y12 inhibitors with hydrophobic mechanisms of action for optimized antiplatelet therapies.