2.7. Molecular dynamics simulations
Molecular dynamic simulation is performed to explore the conformational space of proteins, particularly intermediate states or transitory states that play significant roles in the ligand-protein binding and unbinding. Molecular docking can also be used to determine the binding mechanism of a protein and its ligand. However, the MD simulations not only improve the local steric clashes between protein and ligand, yet also correct and optimize the ligand’s initial mode during molecular docking. Sixteen hundred nanoseconds (ns) simulation was done to study the dynamic behavior of the complex utilizing the AMBER force field [Systems were prepared using an antechamber program of AMBER. The systems were solvated by placing the complexes in a cubic box of 12 Å with a three-point convertible intermolecular potential (TIP3P) water box. The minimization was performed by imposing a 200 kal/mol constraint on the hydrogen atoms for 500 steps, followed by 1000 steps of minimization for the water box. Using Langevin dynamics, the entire system was heated to 300 K at 1 atm for 20 picoseconds and maintained at that temperature [