Bind3P: Optimization of a Water Model Based on Host–Guest Binding Data

We report a water
model, Bind3P (Version 0.1), which was obtained
by using sensitivity analysis to readjust the Lennard-Jones parameters
of the TIP3P model against experimental binding free energies for
six host–guest systems, along with pure liquid properties.
Tests of Bind3P against >100 experimental binding free energies
and
enthalpies for host–guest systems distinct from the training
set show a consistent drop in the mean signed error, relative to matched
calculations with TIP3P. Importantly, Bind3P also yields some improvement
in the hydration free energies of small organic molecules and preserves
the accuracy of bulk water properties, such as density and the heat
of vaporization. The same approach can be applied to more sophisticated
water models that can better represent pure water properties. These
results lend further support to the concept of integrating host–guest
binding data into force field parametrization.