where k B is the Boltzmann constant, T is a temperature weighting factor, n is the number of sampling points and V ref were taken from the OPLS force field, but could also be set to zero. It is also important to note that it is not possible to always perfectly recreate the entire QM potential energy surface hence users should concentrate on relatively low energy regions as these are most likely to be sampled during room temperature simulations. The weighting temperature T can be adjusted to preferentially weight the lowenergy regions of the QM potential energy surface.