After the system setup, an energy minimization with an implementation of the L-BFGS Optimizer 87 was performed for a maximum of 5000 steps. Following, the system was replicated for 11 λ that forms the transformation path between end-state A and end-state B. The transformation is described by a linear coupling between both endstates with the extreme points of 0 and 1. To avoid singularities during the transformations, v2 softcore interactions were applied for the Lennard Jones nonbonded terms with an α of 0.85 and a σ of 1.0. Each replicate was equilibrated with the corresponding λ-value for 1 ns. For the equili-bration and the final production run, a Langevin integrator was used with an integration step of 4 fs, due to the HMR-scheme, and a collision frequency of 1.0ps -1 . The temperature of the system was intrinsically kept at 298.15 K by the Langevin integrator. The pressure was kept at 1 bar with a Monte Carlo Barostat 91,92 that was coupled every 1 ps. Additionally was a λ dependent hamiltonian replica exchange scheme applied. The amount of replicas equaled the amount of λ-points, and after each 1 ps a Metropolis-Hastings-Monte-Carlo move trying to perform an all-to-all exchange scheme on the replicas. The production runs were performed to generate 5 ns simulations.