2.4 Molecular Dynamic Simulation
The MD simulation is widely used to determine the structural stability
of the protein and protein-ligand complexes under physiological
conditions [13]. To evaluate the stability of 2 obtained structures
from docking analysis, molecular dynamic simulation was applied using
GROMACS 4.6.5 suits [14]. GROMOS96 force field and simple point
charge (SPC) as water model was used to generate topology files. All
simulations were analyzed at 343 K. To neutralize each system, some
water molecules were randomly replaced by ions. After being neutralized,
the system’s energy was minimized using the steepest descent algorithm.
Then all systems were simulated for 100 ps under NVT at 300 K and NPT
ensembled at the pressure of 1 bar within periodic boundary conditions
and restraint force of 100 KJ/mol using modified Berendsen thermostat
and Parinello-Rahman barostat algorithms, respectively. The
electrostatic interactions were evaluated using the Particle Mesh Ewald
(PME) algorithm. Ultimately, the MD run was done with no restraint for
50 ns to evaluate the stability of structures.