Spatially Dependent Thermodynamic Integration: A Method to Compute Chemical Potentials of Dense Fluids and Concentrated Liquid Mixtures

Well established computational methods aiming at calculating chemical potentials rely on inserting test particles in the target system. The increase in density or concentration renders this procedure unfeasible, and the use of more sophisticated sampling techniques becomes inevitable. We propose an alternative strategy based on the Hamiltonian adaptive resolution framework. Here, the molecules of the target system, described with the appropriate resolution, are in physical contact with a reservoir of molecules modeled as ideal gas particles. To enforce a uniform density profile across the simulation box, a single-molecule external potential is computed, applied and identified with the excess chemical potential of the target system. We validate the method by computing chemical potentials of various molecular liquids, including aqueous solutions of sodium chloride.