Calculation of the water-octanol partition coefficient of cholesterol for SPC, TIP3P, and TIP4P water

Jorge R Espinosa; Charlie R Wand; Carlos Vega; Eduardo Sanz; Daan Frenkel

doi:10.1063/1.5054056

Calculation of the water-octanol partition coefficient of cholesterol for SPC, TIP3P, and TIP4P water

J Chem Phys. 2018 Dec 14;149(22):224501. doi: 10.1063/1.5054056.

Authors

Jorge R Espinosa¹, Charlie R Wand², Carlos Vega¹, Eduardo Sanz¹, Daan Frenkel²

Affiliations

¹ Departamento de Quimica Fisica, Facultad de Ciencias Quimicas, Universidad Complutense de Madrid, 28040 Madrid, Spain.
² Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.

PMID: 30553262
DOI: 10.1063/1.5054056

Abstract

We present a numerical study of the relative solubility of cholesterol in octanol and water. Our calculations allow us to compare the accuracy of the computed values of the excess chemical potential of cholesterol for several widely used water models (SPC, TIP3P, and TIP4P). We compute the excess solvation free energies by means of a cavity-based method [L. Li et al., J. Chem. Phys. 146(21), 214110 (2017)] which allows for the calculation of the excess chemical potential of a large molecule in a dense solvent phase. For the calculation of the relative solubility ("partition coefficient," log₁₀ $P_{o / w}$ ) of cholesterol between octanol and water, we use the OPLS/AA force field in combination with the SPC, TIP3P, and TIP4P water models. For all water models studied, our results reproduce the experimental observation that cholesterol is less soluble in water than in octanol. While the experimental value for the partition coefficient is log₁₀ $P_{o / w}$ = 3.7, SPC, TIP3P, and TIP4P give us a value of log₁₀ $P_{o / w}$ = 4.5, 4.6, and 2.9, respectively. Therefore, although the results for the studied water models in combination with the OPLS/AA force field are acceptable, further work to improve the accuracy of current force fields is needed.