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Title: Computation of Hydration Free Energies Using the Multiple Environment Single System Quantum Mechanical/Molecular Mechanical Method

Journal Article · · Journal of Chemical Theory and Computation
 [1];  [2];  [1];  [1];  [1];  [3];  [4];  [1];  [5]
  1. National Institutes of Health, National Heart, Lung and Blood Institute, Rockville, MD (United States)
  2. East China Normal Univ., Shanghai (China); NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai (China)
  3. The Ohio State Univ., Columbus, OH (United States)
  4. Univ. of South Florida, Tampa, FL (United States)
  5. Q-Chem Inc., Pleasanton, CA (United States)
+ Show Author Affiliations

A recently-developed MESS-E-QM/MM method (multiple-environment single-system quantum mechanical molecular/mechanical calculations with a Roothaan-step extrapolation) is applied to the computation of hydration free energies for the blind SAMPL4 test set and for twelve small molecules. First, free energy simulations are performed with classical molecular mechanics force field using fixed-geometry solute molecules and explicit TIP3P solvent, then the non-Boltzmann-Bennett method is employed to compute the QM/MM correction (QM/MM-NBB) to the molecular mechanical hydration free energies. For the SAMPL4 set, MESS-E-QM/MM-NBB corrections to the hydration free energy can be obtained 2 or 3 orders of magnitude faster than fully converged QM/MM-NBB corrections, and, on average, the hydration free energies predicted with MESS-E-QM/MM-NBB fall within 0.10–0.20 kcal/mol of full-converged QM/MM-NBB results. Here, out of five density functionals (BLYP, B3LYP, PBE0, M06-2X, and ωB97X-D), the BLYP functional is found to be most compatible with the TIP3P solvent model and yields the most accurate hydration free energies against experimental values for solute molecules included in this study.

Research Organization:
Q-Chem Inc., Pleasanton, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
SC0011297
OSTI ID:
1466797
Journal Information:
Journal of Chemical Theory and Computation, Vol. 12, Issue 1; ISSN 1549-9618
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 41 works
Citation information provided by
Web of Science

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Cited By (7)

Blind prediction of distribution in the SAMPL5 challenge with QM based protomer and pK a corrections journal September 2016
Solvation Free Energy Calculations: The Combination between the Implicitly Polarized Fixed‐charge Model and the Reference Potential Strategy journal August 2019
On the convergence of multi-scale free energy simulations journal November 2017
Multiscale methods in drug design bridge chemical and biological complexity in the search for cures journal April 2018
Hybrid QSPR models for the prediction of the free energy of solvation of organic solute/solvent pairs journal January 2019
A Comparison of QM/MM Simulations with and without the Drude Oscillator Model Based on Hydration Free Energies of Simple Solutes journal October 2018
Dual QM and MM Approach for Computing Equilibrium Isotope Fractionation Factor of Organic Species in Solution journal October 2018

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY