Infinite Dilution Activity Coefficients as Constraints for Force Field Parameterization and Method Development

Molecular simulations begin with an underlying energy model or force field, and from this, can predict diverse physical properties.

However, force fields were often developed with relatively limited datasets, yet accuracy for diverse properties across a broad chemical space is desirable, so tests of such accuracy are particularly important. Here, to this end, we calculate 237 infinite dilution activity coefficients (IDACs), comparing with experimental values from NIST's ThermoML database. We found that calculated IDAC values correlate strongly with experiment (Pearson R of 0.92+/- 0.01), and allow us to identify specific functional groups which appear to present challenges to the force field employed. One potentially valuable aspect of IDACs, as compared to solvation free energies which have been frequently employed as force field tests, is that the same molecules serve both as solutes and solvents in different cases, allowing us to ensure force fields are not overly tuned to one particular environment or solvent.