2.5 Molecular Dynamics Simulation
In order to verify the stability of the compound-protein complexes from
the docking study, in this study, we used GROMACS41,42to do Molecular dynamic simulation (MD). Firstly, from Swissparam web
server43, we obtained topology files and parameters
for the ligands. Placed in a periodic cubic bos with a 1.2nm edge, the
protein-ligand complex was solvated with TIP3P water molecules and 0.145
M NaCl ions. The complex systems was minimized for 5000 steps by the
steepest descent algorithm. The temperature was set at 310K in canonical
ensemble (NVT) and isothermal-isobaric ensemble (NPT). The NVT balance
simulation is a total of 20 ns with a time step of 2 fs. The Lincs
algorithm constrains all keys and 310K temperature settings, similar to
the physiological environment. The NPT operates in balance for 20 ns and
sets the temperature coupling during the simulation. To describe the
chemical scaffold of the protein-ligand complex, the charmm27 was
applied. Neighbor searching cutoff and 3-D PBC for periodic boundary
conditions was performed with Verlet scheme in this 100ns dynamic
simulation. For analyzing the stability of the compound-protein
complexes, we calculate root mean square deviation (RMSD), total energy,
radius of gyrate, solvent accessible solvent area (SASA), root mean
square fluctuation (RMSF), mean square deviation (MSD).