Application of RESP charges to calculate conformational energies, hydrogen bond energies, and free energies of solvation

We apply a new restrained electrostatic potential fit charge model (two-stage RESP) to conformational analysis and the calculation of intermolecular interactions. Specifically, we study conformational energies in butane, methyl ethyl thioether, three simple alcohols, three simple amines, and 1,2-ethanediol as a function of charge model (two-stage RESP us standard ESP) and 1-4 electrostatic scale factor. We demonstrate that the two-stage RESP model with a 1-4 electrostatic scale factor of ∼1/1.2 is a very good model, as evaluated by comparison with high-level ab initio calculations. For methanol and N-methylacetamide interactions with TIP3P water, the two-stage RESP model leads to hydrogen bonds only slightly weaker than found with the standard ESP changes