MÔ HÌNH PHARMACOPHORE CÁC CHẤT CHỦ VẬN VÀ DOCKING TRÊN THỤ THỂ DOPAMIN D2

Abstract

Objectives: Dopamine D2 receptor (D2R) agonists have been shown to be involved in many diseases, such as Parkinson's disease, hyperprolactinemia, and Alzheimer's disease. The building of pharmacophore model and docking model on dopamine 2 receptor makes virtual screening convenient. Methods: Three pharmacophore models were built, including agonist ligands, an antagonist ligand complex, and antagonist ligands. The training set includes 6 agonists, 11 antagonists, and the X-ray crystal structure of D2R (PDB: 6CM4). The test set includes 147 active substances, 108 inactive substances, and 400 decoy substances. Each model was evaluated for accuracy, sensitivity, and specificity, and the best models were compared. The docking model was built based on 6CM4 and assessed through RMSD and binding mode. Results: This study has built a pharmacophore model of D2R agonists, including a positive ionisable feature, a hydrophobic feature, an aromatic ring, and a hydrogen-bond donor. The docking model created meets the requirements with a binding site containing important amino acids such as Asp114, Ser193, and Ser194 and the redocking score is about -31 kJ/mol, with an RMSD ranging from 0.86 to 1.18 Å. Conclusions: The pharmacophore model and docking model have been constructed to meet the specified requirements, are similar to other studies worldwide, and can be applied in virtual screening.