Next Article in Journal
Comparison of Structural and Functional Properties of Starches from the Rhizome and Bulbil of Chinese Yam (Dioscorea opposita Thunb.)
Previous Article in Journal
Gold and Nickel Extended Thiophenic-TTF Bisdithiolene Complexes
Article Menu
Issue 2 (February) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(2), 425; https://doi.org/10.3390/molecules23020425

Effect of Atomic Charges on Octanol–Water Partition Coefficient Using Alchemical Free Energy Calculation

RIKEN Innovation Center, Nakamura Laboratory, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
*
Author to whom correspondence should be addressed.
Received: 19 January 2018 / Revised: 11 February 2018 / Accepted: 14 February 2018 / Published: 15 February 2018
(This article belongs to the Section Medicinal Chemistry)
Full-Text   |   PDF [2015 KB, uploaded 20 February 2018]   |  

Abstract

The octanol–water partition coefficient (logPow) is an important index for measuring solubility, membrane permeability, and bioavailability in the drug discovery field. In this paper, the logPow values of 58 compounds were predicted by alchemical free energy calculation using molecular dynamics simulation. In free energy calculations, the atomic charges of the compounds are always fixed. However, they must be recalculated for each solvent. Therefore, three different sets of atomic charges were tested using quantum chemical calculations, taking into account vacuum, octanol, and water environments. The calculated atomic charges in the different environments do not necessarily influence the correlation between calculated and experimentally measured ∆Gwater values. The largest correlation coefficient values of the solvation free energy in water and octanol were 0.93 and 0.90, respectively. On the other hand, the correlation coefficient of logPow values calculated from free energies, the largest of which was 0.92, was sensitive to the combination of the solvation free energies calculated from the calculated atomic charges. These results reveal that the solvent assumed in the atomic charge calculation is an important factor determining the accuracy of predicted logPow values. View Full-Text
Keywords: MD simulation; thermodynamic integration; solvation environment; atomic charge MD simulation; thermodynamic integration; solvation environment; atomic charge
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Ogata, K.; Hatakeyama, M.; Nakamura, S. Effect of Atomic Charges on Octanol–Water Partition Coefficient Using Alchemical Free Energy Calculation. Molecules 2018, 23, 425.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top