SAMPL6 Octanol-Water Partition Coefficients from Alchemical Free Energy Calculations with MBIS Atomic Charges

02 October 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


In molecular modeling the description of the interactions between molecules forms the basis for a correct prediction of macroscopic observables. Here, we derive atomic charges from the implicitly polarized electron density of eleven molecules in the SAMPL6 challenge using the Hirshfeld-I and Minimal Basis Set Iterative Stockholder(MBIS) partitioning method. These atomic charges combined with other parameters in the GAFF force field and different water/octanol models were then used in alchemical free energy calculations to obtain hydration and solvation free energies, which after correction for the polarization cost, result in the blind prediction of the partition coefficient. From the tested partitioning methods and water models the S-MBIS atomic charges with the TIP3P water model presented the smallest deviation from the experiment. Conformational dependence of the free energies and the energetic cost associated with the polarization of the electron density are discussed.


MBIS atomic charges
Alchemical Free Energy Simulations FESetup
electron density partitioning


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