After proper parametrization of the system, to remove bad contacts, minimization was performed in two stages using a combination of steepest descent (5000 steps) and conjugate gradient (5000 steps) methods. In the first stage water position and conformations are relaxed keeping the protein fixed. Thereafter the whole complex was minimized. Subsequently, the system is gently annealed up to 300K under the NVT ensemble for 50ps. After that, 1ns of density equilibration was performed under an NPT ensemble at a target temperature of 300K and pressure 1 atm by using Langevin thermostat and Berendsen barostat with a collision frequency of 2ps and pressure relaxation time of 1ps. This 1 ns density equilibration is a weakly restrained MD simulation in which the system is slowly released to achieve uniform density after heating under periodic boundary conditions. Then after we remove all the restraints applied before and the system gets equilibrated for 3 ns to get a well-settled pressure and temperature for chemical and conformational analyses. Thereafter, a productive MD simulation was performed using the Monte Carlo barostat for 100 ns for each complex system. We used three different replicas starting from different initial velocities each for 300 ns. Therefore, we performed a total of 300 ns simulations including all three replicas for each system. During all the MD simulations, covalent bonds containing hydrogens were constrained using the SHAKE algorithm, and Particle Mesh Ewald (PME) method was used to treat long-range electrostatic interactions with the cut-off set as 10 Å. All MD simulation was performed with the GPU version of the AMBER 20 package. The MD trajectory analysis was done with the CPPTRAJ 38 module of AMBER20. The visualization of the MD trajectories was performed by VMD . All MD simulations were re-run for 3 different replicas starting from different initial velocities (see SI).