Molecular dynamics simulations of M2 channel in phospholipid bilayers with different thickness

Abstract

Two previous studies showed that M2 channel, a viral protein plays important role in replication of influenza virus, had different conformation after phospholipid bilayers thickness by using site-directed spin-label EPR spectroscopy (SDSL/EPR), one study, the M2 was spin-labeled on N-terminal amino acid residues, another one the M2 was spin-labeled on the C-terminal amino acid residues. Both studies supported each another. The more thickness phospholipid bilayer is the higher spin coupling value. It can be concluded that the conformation of M2 channel depends on phospholipid bilayer thickness. Data got from this technique is ambiguous, spin-spin coupling cannot be distinguishable, diagonal distance pairs or lateral distance pairs. Precise detail on molecular were limited, so computer simulation was required. We used molecular dynamic to study. We simulated and performed embed M2 channel in 3 different thickness phospholipids, DLPC, DMPC and POPC in nature condition (none spin-labeling), C-terminal spin-labeling. For confirmation that of the conformation changing was not cause by freedom of terminal ends, the C-terminal spin-labeling with terminals constrained systems were performed. Instead of the thickness of the membrane, trajectories analysis show that conformational changes were caused by perturbation of spin-labeling compound, MTSSL. In addition, distance between subunit of the protein have no relation to the thickness of the membrane and freedom of the terminal end.