Virtual screening of Indonesian herbal database as adenosine A₂A antagonist using AutoDock and AutoDock vina

Objective: Previous research found that Adenosine A₂A antagonist allows to reduce motor fluctuations, dyskinesia, protect from neurodegenerative disorder in Parkinson's disease in the human brain which is chronic progressive of losing dopaminergic neurons. The aim of this study is to explore Indonesian herbal compounds as Adenosine A₂A inhibitor using virtual screening method. Methods: In this study, virtual screening of Indonesian herbal database as Adenosine A₂A inhibitor was done by AutoDock and AutoDock Vina and was validated by database from A Directory of Useful Decoys: Enhanced (DUD-E). The method was validated by Enrichment Factor (EF) and Area Under Curve (AUC) of Receiver Operating Characteristics (ROC) curve Results: Based on the validation results, grid box that was used in virtual screening using AutoDock is 60 × 60 × 60 with EF1% 16.5869 and AUC 0.8406. The two compounds Chitranone and 3-O-Methylcalopocarpin with binding energy -10.19 and -9.55 kcal/mol, respectively showing interaction with Adenosine A₂A active site at residues ALA63, ILE66, ALA81, LEU85, PHE168, GLU169, MET177, TRP246, LEU249, ASN253 and ILE274. Conclusions: This study concludes that Chitranone and 3-O-Methylcalopocarpin could be proposed to be developed as Adenosine A₂A antagonists.