2.10. Molecular Dynamics Simulation

Molecular dynamics simulations were performed for 50 nanoseconds using Desmond, a Package of Schrödinger LLC [37]. The initial stage of protein and ligand complexes for molecular dynamics simulation were obtained from docking studies. Molecular Docking Studies provide a prediction of ligand binding status in static conditions. Simulations were carried out to predict the ligand binding status in the physiological environment. The protein–ligand complexes were preprocessed using Protein Preparation Wizard or Maestro, which also included optimization and minimization of complexes. All systems were prepared by the System Builder tool. Solvent Model with an orthorhombic box was selected as TIP3P (Transferable Intermolecular Interaction Potential 3 Points). The OPLS_2005 force field was used in the simulation [38]. The models were made neutral by adding counter ions where needed. To mimic the physiological conditions, 0.15 M salt (NaCl) was added. The NPT ensemble (Isothermal-Isobaric: moles (N), pressure (P), and temperature (T) are conserved) with 300 K temperature and 1 atm pressure was select for complete simulation. The models were relaxed before the simulation. The trajectories were saved after every 50 ps for analysis, and the stability of simulations was evaluated by calculating the root mean square deviation (RMSD) of the protein and ligand over time.