Cholesterol effects on the phosphatidylcholine bilayer polar region: A molecular simulation study

A molecular dynamics (MD) simulation of a fully hydrated, liquid-crystallin e dimyristoylphosphatidylcholine (DMPC)-Chol bilayer membrane containing si milar to 22 mol% Chol was carried out for 4.3 ns. The bilayer reached therm al equilibrium after 2.3 ns of MD simulation. A 2.0-ns trajectory generated during 2.3-4.3 ns of MD simulation was used for analyses to determine the effects of Chol on the membrane/water interfacial region. In this region, 7 0% of Chol molecules are linked to DMPC molecules via short-distance intera ctions, where the Chol hydroxyl group (OH-Chol) is 1) charge paired to meth yl groups of the DMPC choline moiety (similar to 34%), via the hydroxyl oxy gen atom (Och); 2) water bridged to carbonyl (similar to 19%) and nonester phosphate (similar to 14%) oxygen atoms, via both Och and the hydroxyl hydr ogen atom (Hch); and 3) directly hydrogen (H) bonded to carbonyl (similar t o 11%) and nonester phosphate (similar to 5%) oxygen atoms, via Hch (simila r to 17% of DMPC-Chol links are multiple). DMPC's gamma-chain carbonyl oxyg en atom is involved in 44% of water bridges and 51% of direct H bonds forme d between DMPC and Chol. On average, a Chol molecule forms 0.9 links with D MPC molecules, while a DMPC molecule forms 2.2 and 0.3 links with DMPC and Chol molecules, respectively. OH-Chol makes hydrogen bonds with 1.1 water m olecules, preferentially via Hch. The average number of water molecules H b onded to the DMPC headgroup is increased by 7% in the presence of Chol. The se results indicate that inclusion of Chol decreases interlipid links and i ncreases hydration in the polar region of the membrane.