Theoretical study of the interactions between the first transmembrane segment of NS2 protein and a POPC lipid bilayer

•Residues R3, K27, S23 and H25 are key elements in establishing the conformation of TM1 inside the membrane.•The peptide forms a stable α-helix (aa 12-21) connected to N-terminal haft in POPC bilayer.•TM1 induces the ordering of lipid and does not destabilize the lipid bilayer system.•A hydrophobic mismatch was observed in this system.•Binding free energy profile of TM1 to the membrane was determined.

Non-structural protein 2 (NS2) plays a crucial role in the hepatitis C virus (HCV) assembly. NS2 was predicted to be composed of three transmembrane (TM) segments. However, the mechanism of interactions between TM segments of NS2 and surrounding lipid environment remains unclear. Molecular dynamics simulations were applied to investigate the conformation and orientation of the first transmembrane segment (TM1) as well as the interactions of TM1 with a zwitterionic POPC lipid bilayer which identifies several key residues that stabilize the position of TM1 within the membrane. Along with the charged residues R3 and K27, the S23 and H25 were found to be the key elements in establishing the conformation of TM1 inside the membrane. The peptide forms a stable α-helix (the sequence 12-21) connected to N-terminal haft in POPC bilayer. The results also reveal that TM1 induces the ordering of lipid and does not destabilize the lipid bilayer system. The hydrophobic mismatch in which the segment tilts an angle along the membrane normal was observed in this system. The binding free energy profile of TM1 to the membrane was also estimated using umbrella sampling.

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