Hybrid Integral‐Equation/Simulation Models: From Complexation Thermodynamics to Direct Free Energies

Statistical-mechanical integral equation theory, an approximate methodology for computing distribution functions and thermodynamic properties of the liquid state, can be advantageously combined with molecular simulations to overcome inherent limitations of both approaches. This Concept discusses a number of conceptual applications that illustrate the capabilities of hybrid models: A study of complex formation in solution by explicit simulation of only the solute molecules, the correction of artefacts induced by truncated potentials, and an approach to the direct computation of free energies from a simulation of a single state.