Lipophilicity of Coarse-Grained Cholesterol Models

Autor(es)

Fornasier, Franccesca ^[1] ; Souza, Lucas M. P. ^[1] ; Souza, Felipe R. ^[1] ; Reynaud, Franceline ^{[2, 3]} ; Pimentel, Andre S. ^[1]

Afiliação do(s) autor(es)

^[1] Pontificia Univ Catolica Rio de Janeiro, Dept Quim, BR-22453900 Rio De Janeiro, RJ - Brazil

^[2] Univ Paris Saclay, Inst Galien Paris Sud, CNRS 8612, F-92290 Chatenay Malabry, Malabry - France

^[3] Univ Fed Rio de Janeiro, Fac Farm, BR-21941902 Rio De Janeiro, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CHEMICAL INFORMATION AND MODELING; v. 60, n. 2, p. 569-577, FEB 2020.
• Citações Web of Science: 1

Resumo

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. (AU)

• Processo FAPESP: 14/50983-3 - INCT 2014: fluidos complexos
• Beneficiário: Antonio Martins Figueiredo Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático