Parametrization of an Orbital-Based Linear-Scaling Quantum Force Field for Noncovalent Interactions

We
parametrize a linear-scaling quantum mechanical force field
called mDC for the accurate reproduction of nonbonded interactions.
We provide a new benchmark database of accurate ab initio interactions
between sulfur-containing molecules. A variety of nonbond databases
are used to compare the new mDC method with other semiempirical, molecular
mechanical, ab initio, and combined semiempirical quantum mechanical/molecular
mechanical methods. It is shown that the molecular mechanical force
field significantly and consistently reproduces the benchmark results
with greater accuracy than the semiempirical models and our mDC model
produces errors twice as small as the molecular mechanical force field.
The comparisons between the methods are extended to the docking of
drug candidates to the Cyclin-Dependent Kinase 2 protein receptor.
We correlate the protein–ligand binding energies to their experimental
inhibition constants and find that the mDC produces the best correlation.
Condensed phase simulation of mDC water is performed and shown to
produce O–O radial distribution functions similar to TIP4P-EW.