Molecular dynamics

After understanding the rigid docking of the ligand–protein complex, its flexible docking was studied via molecular dynamics (MD) to mimic the biological system. MD simulations were implemented via the Desmond tool of Schrödinger Drug Design Suite. Based on the docking score and free binding energy, two ligands were carried forward for MD simulation for 50 ns to study their stability. The three steps performed for MD simulation were building the system, minimization, and the MD simulation itself. The docked ligand–protein complex was selected, and the system was modeled by a predefined solvent system—SPC under the orthorhombic boundary conditions. Any negative charges on the model were neutralized with sodium ions and the model was subjected to energy minimization until a gradient threshold of 25 kcal/mol/Å was achieved at a temperature of 300 K and 1 bar pressure via NPT ensemble class. On conduction of the MD simulation, the trajectory was recorded and the stability of the complex was evaluated by the Protein and Ligand RMSD (Root-Mean-Square Deviation) fluctuations, Protein–Ligand interactions, and contacts with various amino acids using the Simulation Event Analysis tool of Desmond (Bowers et al. 2006).