After proper parameterizations and setup, the resulting system's geometries were minimized (5000 steps for steepest descent and 10,000 steps for conjugate gradient) to remove the poor contacts and relax the system. The systems were then gently annealed from 10 to 300 K under canonical ensemble for 50 ps with a weak restraint of 5 kcal/mol/Å 2 . Subsequently, the systems were maintained for 1 ns of density equilibration under isothermal-isobaric ensemble at the target temperature of 300K and the target pressure of 1.0 atm using a Langevin-thermostat and a Berendsen barostat with a collision frequency of 2 ps and a pressure relaxation time of 1 ps, and with a weak restraint of 1 kcal/mol/Å 2 . Thereafter, we removed all restraints applied during heating and density dynamics and further equilibrated the systems for ~3 ns to obtain well-settled pressure and temperature for conformational and thermodynamical analyses. This was followed by a productive MD run of 100 ns for each system. We used three different replicas starting from different initial velocities each for 100 ns. Therefore, we performed a total of 300 ns simulations including all three replicas for each system. During all MD simulations, the covalent bonds containing hydrogen were constrained using SHAKE , and a particle mesh Ewald (PME) was used to treat long-range electrostatic interactions. We used an integration step of 2 fs during the entire simulation. All MD simulations were performed with the GPU version of the Amber 20 package. The analyses of the trajectories were based on the most populated trajectories (100ns) from the MD simulations of all three replicas (100𝑛𝑠 × 3), which provides an accurate means to represent the statistically most significant structures during MD sampling. For doing so, firstly, we seamed all replicas together using the Cpptraj module of Amber, and thereafter, we performed clustering of MD trajectories using the hieragglo algorithm implemented in Cpptraj.