(375f) Molecular Density Functional Theory for Multiscale Modeling of Hydration Free Energy

Molecular
density functional theory for multiscale modeling of hydration free energy

Shijie
Sheng, Jia Fu and Jianzhong Wu

Department
of Chemical and Environmental Engineering, University of California, Riverside,
California 92521, USA

ABSTRACT

Recent developments in physical
and computer sciences enable quantitative predictions of chemical reactions and
thermodynamic data from first principles by multiscale modeling. The
hierarchical approach integrates different theoretical frameworks ranging from
those describing phenomena at the electronic length and time scales to those
pertinent to complex biomolecular systems and macroscopic phase transitions,
promising broad applications to problems of practical concern. Whereas
multiscale modeling has been emerging as a popular computational tool for
engineering applications, the connection between calculations at different
scales is far from being coherent, and the multiple choices of
quantum/classical methods at each scale renders numerous combinations that have
been rarely calibrated against extensive experimental data. In this work, we
have examined a multiscale procedure for predicting the solvation free energies
of a large set of small molecules in liquid water at ambient
conditions. Using the experimental data for the hydration free energies as
the benchmark, we find that the theoretical results are sensitive to the
selection of quantum-mechanical methods for determining atomic charges and
solute configurations, the assignment of the force-field parameters in
particular the atomic partial charges, and approximations in the
statistical-mechanical calculations. Because of significant uncertainties in
quantum-mechanical calculations and the semi-empirical nature of force-field
models, computational efficiency makes the classical density functional theory
a valuable alternative to molecular simulations for future development and
application of multiscale modeling methods.