The equilibration procedure included an NVT and an NPT equilibration, lasting 1 ns, respectively. The Parrinello-Rahman barostat was used for the latter, the same as for the production run, which lasted 12 ns. Equations of motions were integrated with the leap-frog stochastic dynamics integrator. The interaction of the fragments with their environment was gradually decoupled, with equidistant steps of ∆λ = 0.05. The aforementioned equilibrium procedure was carried out for each individual lambda step. Since only neutral fragments were considered, van der Waals interactions were the only type of interaction present in the system. The corresponding potentials were modified with "soft-core" potentials, using a soft-core parameter of α = 0.5. Finally, the transfer free energies were calculated from the difference between two solvation free energies: ∆G S1→S2 = ∆G S1→∅ -∆G S2→∅ . The solvationfree energies were calculated with the help of the Bennett acceptance ratio method , using the GROMACS tool gmx bar.