Lipophilicity of Coarse-Grained Cholesterol Models

The lipophilicity of cholesterol was investigated by using coarse-grained molecular dynamics and umbrella sampling. The previous coarse-grained cholesterol models in the literature are more hydrophobic than our model. The Gibbs free energy of transferring cholesterol from the octanol phase to water phase (Delta G(o/w)) was 11.88 +/- 0.08 kcal mol(-1), and the octanol-water partitioning coefficient (logP) was estimated to be 8.72 +/- 0.06. The latter is in agreement with the logP values found by bioinformatics, which are standard methods to predict the lipophilicity, giving excellent octanol/water partitioning coefficients compared with experimental ones for different molecules. We also performed the first experimentally direct measurement of this important property for cholesterol. The experimental octanol/water partitioning coefficient of cholesterol was measured to be 8.86 +/- 0.79, which is in excellent agreement with our calculated logP value from our parametrized coarse-grained cholesterol model. This shows the significance of systematic optimization of the lipophilicity for developing coarse-grain models of important biomolecules with complicated molecular structures and hydrophobic character like cholesterol.