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<p>Partition coefficients serve in various areas as pharmacology and environmental sciences to predict the hydrophobicity of different substances. Recently, they have been
also used to address the accuracy of force fields for various organic compounds and
specifically the methylated DNA bases. In this study atomic charges were derived
by different partitioning methods (Hirshfeld and Minimal Basis Iterative Stockholder)
directly from the electron density obtained by electronic structure calculations in vac-
uum, with an implicit solvation model or with explicit solvation taking the dynamics of
the solute and the solvent into account. To test the ability of these charges to describe
electrostatic interactions in force fields for condensed phases the original atomic charges
of the AMBER99 force field were replaced with the new atomic charges and combined
with different solvent models to obtain the hydration and chloroform solvation free
energies by molecular dynamics simulations. Chloroform-water partition coefficients
derived from the obtained free energies were compared to experimental and previously
reported values obtained with the GAFF or the AMBER-99 force field. The results
show that good agreement with experimental data is obtained when the polarization
of the electron density by the solvent has been taken into account deriving the atomic
charges of polar DNA bases and when the energy needed to polarize the electron den-
sity of the solute has been considered in the transfer free energy. These results were
further confirmed by hydration free energies of polar and aromatic amino acid side
chain analogues. Comparison of the two partitioning methods Hirsheld-I and Minimal
Basis Iterative Stockholder (MBIS) revealed some deficiencies in the Hirshfeld-I method
related to nonexistent isolated anionic nitrogen pro-atoms used in the method. Hydration free energies and partitioning coefficients obtained with atomic charges from the
MBIS partitioning method accounting for polarization by the implicit solvation model
are in good agreement with the experimental values. </p>
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Choosing a solvation model for simulating reactions in KOH(KOBut)/DMSO superbasic media
