Atomistic MD Simulations of n‐Alkanes in a Phospholipid Bilayer: CHARMM36 versus Slipids

Abstract

AbstractLinear alkanes (n‐alkanes) are chemically the most simple linear hydrophobic molecules in nature. Studying the incorporation of n‐alkanes into lipid membranes is therefore a good starting point toward understanding the behavior of hydrophobic molecules in lipid membranes and to assess how accurately molecular dynamics models describe such systems. Here, the miscibility and structure of different n‐alkanes—n‐decane (C10), n‐eicosane (C20), and n‐triacontane (C30)—in dipalmitoylphosphatidylcholine membranes are investigated using two of the most used force fields for lipid membrane molecular dynamics simulations (CHARMM36 and Slipids). The n‐alkanes are miscible in the membrane up to a critical volume fraction, ϕc, that depends on the force field interaction parameters used. ϕc is dependent on alkane chain length only for the model with more disordered chains (Slipids). Below ϕc, a comparison with 2H nuclear magnetic resonance (NMR) spectra indicates that a more realistic structure of the longer alkane molecules (C20 and C30) is obtained using the Slipids force field. On the other hand, for the shorter alkane (C10), Slipids simulations underestimate molecular order and CHARMM36 simulations enable a precise prediction of its experimental spectrum. The predicted 2H NMR spectra are highly sensitive to 1–4 electrostatic interactions, and suggest that a reduction of the partial charges of the longer alkanes and acyl chains in CHARMM36 results in a better performance. The results presented indicate that lipid membranes with incorporated alkanes are highly valuable systems for the validation of force fields designed to perform lipid membrane simulations.