2.4 Molecular Docking and Ligand Receptor Binding analysis
The docking analysis of pdb structures of 2-deoxyglucose and its analogue (1, 3, 4, 6-Tetra-O-acetyl-2-deoxy-D-glucopyranose) with viral receptors (spike glycoprotein, viral nuclease and viral main protease) was carried by Hex Cuda 8.0.0 software. Receptor and Ligand files were imported in the software (Harika et al., 2017). The grid dimension of docking was defined according the to the binding site analysis of DoG Site Scorer (Volkamer et al., 2012). Graphic settings and Docking parameters were customized so as to calculate the binding energies (E values) of ligand receptor docking. The parameters used for the docking process were set as (i) Correlation type: Shape + Electro + DARS, (ii) FFT mode: 3D fast lite, (iii) Grid Dimension: 0.6, (iv) Receptor range: 180°, (v) Ligand range: 180°, (vi) Twist range: 360°. The best docked conformations with lowest docking energy were selected for further MD simulations using Pose View for creating pose depictions of selected ligand-receptor binding (Ezat et al., 2014). Molecular Docking and MD simulations for the standard chemotherapeutic agents (lopinavir, favipiravir, hydroxychloroquine) were also conducted. The MM-PBSA method was used to compute the binding free energy of receptor-ligand docking during simulation. In this study, the binding free energy of the receptors to ligands was calculated using the GROMACS tool, wherein the binding free energy of the receptor and ligand was defined as
ΔGbinding = ΔGcomplex – (ΔGreceptor + ΔGligand)
For each subunit, the free energy, G, can be presented as summation of mechanical potential energy (Electrostatic and Vander Waals interaction) and solvation free energy (Gpolar + Gnonpolar), wherein the total entropy is excluded from the total value (Weis et al., 2006).