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research article

Prediction of aqueous free energies of solvation using coupled QM and MM explicit solvent simulations

Sadowsky, Daniel  
•
Arey, J. Samuel  
April 21, 2020
Physical Chemistry Chemical Physics

A method based on molecular dynamics simulations which employ two distinct levels of theory is proposed and tested for the prediction of Gibbs free energies of solvation for non-ionic solutes in water. The method consists of two additive contributions: (i) an evaluation of the free energy of solvation predicted by a computationally efficient molecular mechanics (MM) method; and (ii) an evaluation of the free energy difference between the potential energy surface of the MM method and that of a more computationally intensive first-principles quantum-mechanical (QM) method. The latter is computed by a thermodynamic integration method based on a series of shorter molecular dynamics simulations that employ weighted averages of the QM and MM force evaluations. The combined computational approach is tested against the experimental free energies of aqueous solvation for four solutes. For solute-solvent interactions that are found to be described qualitatively well by the MM method, the QM correction makes a modest improvement in the predicted free energy of aqueous solvation. However, for solutes that are found to not be adequately described by the MM method, the QM correction does not improve agreement with experiment. These preliminary results provide valuable insights into the novel concept of implementing thermodynamic integration between two model chemistries, suggesting that it is possible to use QM methods to improve upon the MM predictions of free energies of aqueous solvation.

  • Details
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Type
research article
DOI
10.1039/d0cp00582g
Web of Science ID

WOS:000529178800032

Author(s)
Sadowsky, Daniel  
Arey, J. Samuel  
Date Issued

2020-04-21

Publisher

ROYAL SOC CHEMISTRY

Published in
Physical Chemistry Chemical Physics
Volume

22

Issue

15

Start page

8021

End page

8034

Subjects

Chemistry, Physical

•

Physics, Atomic, Molecular & Chemical

•

Chemistry

•

Physics

•

quantum-mechanical calculations

•

henrys law coefficients

•

temperature-dependence

•

dynamics

•

models

•

water

•

exchange

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
IIE  
Available on Infoscience
May 17, 2020
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/168789
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