Inhibiting Adenosine A2A Receptors as a Treatment for Parkinson’s Disease

Abstract

This study aims to find a new drug that has the potential to block the adenosine A2A receptor as a treatment for Parkinson's disease. The research data consisted of the 3-dimensional structure of the A2A receptor (PDB ID: 5IU4) and the crystal structure of the human (Homo sapiens) A2A receptor complex with ZM241385. The database of the testing compounds was 12 ZINC Natural products consisting of 151,837 compounds. In addition, 50 active compounds as a positive control in the validation of the virtual screening. Virtual screening modeling based on pharmacophore and molecular docking. The validated pharmacophore model was used for the virtual screening of compounds in the ZINC Natural Product Database. The validated molecular docking model was used for virtual screening of all docking parameters to the active and the decoy set compounds to the receptor. The results showed that the virtual screening with the pharmacophore model found 321 new drugs, while the molecular docking model found 50 new drugs. In this case, as a drug that can block adenosine A2A receptors. The best drugs to treat Parkinson's disease are ZINC38932599 and ZINC98365141 because these drugs can produce -11.9 Kcal/mol as the lowest ∆G value.