Steering a solute between coexisting solvation states: calculation of free energy differences in the adaptive resolution method

In the adaptive resolution method, it is possible to represent molecules with atomistic resolution in a simulation subregion and as ideal gas particles in a large reservoir. To enforce a uniform density profile across the simulation box, an external potential is applied and identified with the system's excess chemical potential. Indeed, atomistic and ideal gas images coexist at a constant temperature, volume, and chemical potential.

In this context, we present a method to calculate solvation free energies (SFEs) [1]. The idea is to steer the solute between coexisting solvation states, represented by incorporating solvent and ideal gas at a constant chemical potential. At finite pulling speeds, the applied work gives SFEs via non-equilibrium relations, whereas at infinitely slow pulling, the calculation is equivalent to a thermodynamic integration. Results for small molecules well agree with literature data and pave the way to systematic studies of arbitrarily large and complex molecules.

[1] Heidari et.al., JCP 151, 144105 (2019)