The surface site interaction point approach to non-covalent interactions

. By considering the free energies of all possible pairing interactions between all SSIPs in a molecular ensemble, it is possible to calculate the speciation of all intermolecular interactions and hence predict thermodynamic properties using the SSIMPLE algorithm. SSIPs have been used to describe both the solution phase and the solid state and provide accurate predictions of partition coefficients, solvent effects on association constants for formation of intermolecular complexes, and the probability of cocrystal formation. SSIPs represent a simple and intuitive tool for describing the relationship between chemical structure and non-covalent interactions with sufficient accuracy to understand and predict the properties of complex molecular ensembles without the need for computationally expensive simulations.