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).