Free energy calculations of pharmaceutically important properties

When determining the biochemical function of a proposed new drug it is useful to be able to calculate a number of properties which regulate its behaviour. By using the Free Energy Perturbation method incorporated into molecular dynamics, both on its own and in conjunction with quantum mechanical calculations, we have calculated redox potentials, pKa s, tautomer ratios and partition coefficients on model systems.

This paper reviews the techniques currently being used to perform such calculations and presents the results for a number of different systems. The accuracy with which the properties are determined is most encouraging and suggests that useful calculations on realistic systems are now possible, and will play a major role in drug-design in the future.