The electronegativity equalization method and the charge sensitivity analysis, both in the atom-in-molecule resolution, are adapted to complex supramolecular systems. The combination of these methods with the Monte Carlo simulation technique results in a tool that allows one to determine simultaneously the equilibrium (intermolecular) structure as well as the charge distribution of such systems. Furthermore, information about the reactivity of molecules in interaction with a complex environment, e.g. a solvent, can be obtained. The possibilities of the method are illustrated with examples of water and cation-water clusters as well as the interaction of water with different kinds of zeolite framework moieties.