After system setup, we performed a two-stage minimization to remove the unfavorable contacts. First, we minimized the solvent with the enzyme held fixed, and then we conducted a complete complex minimization wherein we utilized a 5000-step steepest descent, followed by a 5000-step conjugate gradient algorithm. Thereafter, systems were gently heated from 0 K to 300 K for 50 ps at the NVT ensemble, followed by an equilibration of 3 ns at the targeted temperature and pressure. The constant temperature of 300 K and the pressure of 1.0 atm were maintained using Langevin thermostat and Berendsen barostat , respectively with a collision frequency of 2 ps and a pressure relaxation time of 1ps. The equilibrated system was then used to perform 100 ns of production MD simulation, employing multitrajectory approach wherein the simulation was restarted after each 50 ns at the random velocity. Monte Carlo barostat was used for the production MD simulation. In addition, replica simulations were carried out to remove any false implications of the results. The SHAKE algorithm was implemented to constrain the covalent hydrogen bonds and Particle Mesh Ewald (PME) algorithm was used to treat the long-range electrostatic interactions during all MD simulations. We used an integration step of 2 fs during the entire simulation. All MD simulations were performed using the GPU-accelerated version of AMBER20 software . The inbuilt CPPTRAJ module of AMBER20 was used to post-process the trajectories. The visualizing software VMD 27 , Chimera , and PYMOL were used for further analyzing the MD trajectories. Furthermore, we also performed the adaptive steered MD simulation (ASMD) and details of such simulation was relegated to SI (cf. S.1.).