Akar Kuning (Arcangelisia Flava) As Neuraminidase Inhibitor: Molecular Docking And Pharmacophore Optimization Approach
Mohammad Rizki Fadhil Pratama · 2017
Objectives: This study aims to find a relationship between secondary metabolites of akar kuning and neuraminidase (NA) with molecular docking study and also to determine the most potent NA inhibitor from metabolites of akar kuning.Methods: All ligands were sketched and optimized using Gaussian 03W with Hartree-Fock method basis sets 6-311G.Molecular docking was performed using AutoDock 4.2.6 toward NA in complexes with oseltamivir, a known NA inhibitor as a co-crystal ligand.The main parameter used was the free energy of binding (ΔG) and dissociation constant (K i ) as affinity marker.Pharmacophore optimization was conducted on metabolite with the highest affinity to assess the main pharmacophore with the highest influence.Results: Fibleucin provided the most negative ΔG and the lowest K i toward NA with -8.12 kcal/mol and 1.11 µM, respectively.Further pharmacophore optimization of fibleucin reveals that ether group at position number 25 had the highest influence toward fibleucin affinity and might be considered as the main pharmacophore of fibleucin as NA inhibitor.Conclusion: in silico molecular docking and pharmacophore optimization results indicated that fibleucin could be considered as NA inhibitor and should be potential to be developed as antiinfluenza particularly to H5N1 with oseltamivir resistance.