Multipolar Ewald Methods, 2: Applications Using a Quantum Mechanical Force Field

A fully quantum mechanical force
field (QMFF) based on a modified
“divide-and-conquer” (mDC) framework is applied to a
series of molecular simulation applications, using a generalized Particle
Mesh Ewald method extended to multipolar charge densities. Simulation
results are presented for three example applications: liquid water, p-nitrophenylphosphate reactivity in solution, and crystalline N,N-dimethylglycine. Simulations of liquid
water using a parametrized mDC model are compared to TIP3P and TIP4P/Ew
water models and experiment. The mDC model is shown to be superior
for cluster binding energies and generally comparable for bulk properties.
Examination of the dissociative pathway for dephosphorylation of p-nitrophenylphosphate shows that the mDC method evaluated
with the DFTB3/3OB and DFTB3/OPhyd semiempirical models bracket the
experimental barrier, whereas DFTB2 and AM1/d-PhoT QM/MM simulations
exhibit deficiencies in the barriers, the latter for which is related,
in part, to the anomalous underestimation of the p-nitrophenylate leaving group pKa. Simulations
of crystalline N,N-dimethylglycine
are performed and the overall structure and atomic fluctuations are
compared with the experiment and the general AMBER force field (GAFF).
The QMFF, which was not parametrized for this application, was shown
to be in better agreement with crystallographic data than GAFF. Our
simulations highlight some of the application areas that may benefit
from using new QMFFs, and they demonstrate progress toward the development
of accurate QMFFs using the recently developed mDC framework.