A final consideration to be made when deriving the non-bonded parameter set is how to treat atoms with significant anisotropy in their electron density, such that an atom-centred point charge gives a poor approximation to the full QM electrostatic potential at the surface of the molecule. Such situations are commonly treated in MM force fields using an offcentre charge (or "virtual site"), as used in, for example, the TIP4P water model 60 and various treatments of lone-pairs and σ-holes in common force fields. In keeping with our general force field philosophy, we previously proposed a method to derive the positions and magnitudes of off-site charges, where required, directly from the partitioned QM electron density. Full details are given elsewhere, but in brief the charges are positioned to minimise the quantity: