Minimal Basis Iterative Stockholder Decomposition with Multipole Constraints.

The minimal basis iterative Stockholder (MBIS) decomposition of molecular electron densities into atomic quantities is an attractive approach for deriving electrostatic parameters in force fields. The MBIS-derived atomic charges, however, in general tend to overestimate the molecular dipole and quadrupole moments by ∼10%. We show that it is possible to derive a constrained MBIS model where the atomic charges or a combination of atomic charges and dipoles exactly reproduce the molecular dipole and quadrupole moments for molecules. The atomic multipole moments derived by the constrained procedure are better at reproducing the molecular electrostatic potential (ESP) than the unconstrained atomic multipole moments. They are, furthermore, significantly less conformationally dependent than atomic charges obtained by fitting to the molecular electrostatic potential.