Molecular dynamics study of hydrated 1,2-dilignoceroylphosphatidylcholine (DLGPC) monolayer and virus protein U (Vpu)/membrane/water systems

Constant normal pressure, constant surface tension and constant temperature (NP_NγT) molecular dynamics (MD) simulations have been performed on 1,2-dilignoceroylphosphatidylcholine (DLGPC) Langmuir monolayer and Virus Protein U (Vpu)/DLGPC/water monolayer systems. NP_NγT ensemble was employed to reproduce the experimental observations, such as area/lipid, since surface tension is an essential factor in determining the monolayer structure. Data analysis on DLGPC/water monolayer shows that various liquid-condensed phase properties of the monolayer have been well reproduced from the simulation, indicating that surface tension 22.9mN/m used in the simulation is an appropriate condition for the condensed phase NP_NγT simulation. The simulation results suggest that this long-chain phospholipid monolayer shares many structural characteristics with typical short-chain 1,2-diacylphosphatidylcholine systems. Furthermore, it was found that DLGPC/water monolayer has almost completely rotationally disordered acyl chains which have not been observed so far in short-chain 1,2-diacylphosphatidylcholine/water bilayers. The simulation indicates the good biological relevance of the DLGPC/water monolayer which might be useful in protein/lipid studies to reveal protein structure and protein-lipid interactions in a membrane environment.; Vpu is an accessory membrane protein encoded by human immunodeficiency virus type 1 (HIV-1). Various experimental studies have shown that transmembrane domain of Vpu has a helical conformation and cytoplasmic domain adopts the helix-loop-helix-turn motif. This 3.5-ns molecular dynamics simulation of Vpu in lipid membrane environment has fully reproduced these structural characteristics. Membrane propensities of two amphipathic helices in cytoplasmic domain are further compared here to understand better their complicated orientational behavior known from the experiments. This study first reveals that the highly conserved loop region in cytoplasmic domain can be closely associated with membrane surface. It is known from the simulation that Vpu is associated with 34 lipids in this Langmuir monolayer. The lipids that are located between Vpu transmembrane helix and the first helix in cytoplasmic domain are pushed up by Vpu. These elevated lipids have increased P-N tilt angle for head groups yet with unchanged acyl-chain tilt angle compared with lipids that do not interact with Vpu. This study verifies the significance of applying MD simulation in refining protein structure and revealing detailed protein-lipid interaction in membrane/water environment.