Cost-Effective Method for Free-Energy Minimization
in Complex Systems with Elaborated Ab Initio Potentials
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Abstract
We
describe a method to locate stationary points in the free-energy
hypersurface of complex molecular systems using high-level correlated <i>ab initio</i> potentials. In this work, we assume a combined
QM/MM description of the system although generalization to full <i>ab initio</i> potentials or other theoretical schemes is straightforward.
The free-energy gradient (FEG) is obtained as the mean force acting
on relevant nuclei using a dual level strategy. First, a statistical
simulation is carried out using an appropriate, low-level quantum
mechanical force-field. Free-energy perturbation (FEP) theory is then
used to obtain the free-energy derivatives for the target, high-level
quantum mechanical force-field. We show that this composite FEG-FEP
approach is able to reproduce the results of a standard free-energy
minimization procedure with high accuracy, while simultaneously allowing
for a drastic reduction of both computational and wall-clock time.
The method has been applied to study the structure of the water molecule
in liquid water at the QCISD/aug-cc-pVTZ level of theory, using the
sampling from QM/MM molecular dynamics simulations at the B3LYP/6-311+G(d,p)
level. The obtained values for the geometrical parameters and for
the dipole moment of the water molecule are within the experimental
error, and they also display an excellent agreement when compared
to other theoretical estimations. The developed methodology represents
therefore an important step toward the accurate determination of the
mechanism, kinetics, and thermodynamic properties of processes in
solution, in enzymes, and in other disordered chemical systems using
state-of-the-art <i>ab initio</i> potentials