Molecular Docking and Dynamics Simulation Studies to Predict Multiple Medicinal Plants' Bioactive Compounds Interaction and Its Behavior on the Surface of DENV-2 E Protein

Abstract

The envelope protein (E) is a required fusion class II protein for DENV fusion. We use galangin and kaempferide, two active chemicals obtained from commonly used plants in Indonesia. Normal physiological parameters were used to a docking and 1000 ps molecular dynamic analysis. The galangin and kaempferide binding sites fluctuatingly changed throughout the experiment. However, chloroquine retains contact with fusion loops due to its lower ligand mobility, whereas both other drugs lose contact with hydrophobic pockets. In contrast, the ligand structure of the two active molecules is more stable. The RMSF simulation of the protein E residues revealed changes of less than 2 Å. In a 1000 ps simulation, all tested compounds form stable complexes with protein E, indicating that the two active compounds may be expected as DENV-2 E protein fusion inhibitors, despite chloroquine inhibiting in a manner that is distinctively tied to its interaction domains.