Molecular dynamics simulation of human immunodeficiency virus protein U (Vpu) in lipid/water Langmuir monolayer

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Abstract
Virus protein U (Vpu) is an accessory membrane protein encoded by human immunodeficiency virus type 1 (HIV-1). Various NMR and CD studies have shown that the transmembrane domain of Vpu has a helical conformation and that the cytoplasmic domain adopts the helix-loop-helix-turn motif. This 3.5-ns molecular dynamics (MD) simulation of Vpu in a lipid/membrane environment has fully reproduced these structural characteristics. Membrane propensities of two amphipathic helices in the cytoplasmic domain are further compared here to understand better their complicated orientational behavior known from experiment. This study first reveals that the highly conserved loop region in the cytoplasmic domain can be closely associated with the 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 the Vpu transmembrane helix and the first helix in the cytoplasmic domain are pushed up by Vpu. These elevated lipids have increased P-N tilt angles for the head groups but unchanged acyl-chain tilt angles 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. Figure XZ view of a snapshot of Vpu/DLGPC/water system after 3.5 ns NP(N)gamma T MD simulation. Coloring scheme: Vpu, red; C, green; H, pink; N, blue; O, orange; P, magenta; water, light blue

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