Hydrogen-bonding patterns of cholesterol in lipid membranes

Correlation between the rotation of the cholesterol hydroxyl group and the formation of hydrogen bonds with its lipid environment is examined through molecular dynamics (MD) simulations and compared with recently reported NMR experiments. All atom MD simulations of a fully hydrated 1:2 cholesterol–dimyristoylphosphatidylcholine bilayer have been performed. Precise reproduction of the cholesterol cell parameters via simulation of its P1-group crystal validates the force field utilized. The lipid–cholesterol hydrogen-bonding pattern reflects the coexistence of alternative dimer motifs with comparable conformer populations, in line with the estimated free energy differences for the rotamers of the cholesterol CO bond.