Transmembrane domains of viral ion channel proteins: A molecular dynamics simulation study

Nanosecond molecular dynamics simulations in a fully solvated phospholipid bilayer have been performed on single transmembrane alpha-helices from thre e putative ion channel proteins encoded by viruses: NB (from influenza B), CM2 (from influenza C), and Vpu (from HIV-1). alpha-Helix stability is main tained within a core region of ca. 28 residues for each protein. Helix pert urbations are due either to unfavourable interactions of hydrophobic residu es with the lipid headgroups or to the need of the termini Of short helices to extend into the surrounding interfacial environment in order to form H- bonds. The requirement of both ends of a helix to form favourable interacti ons with lipid headgroups and/or water may also lead to tilting and/or kink ing of a transmembrane alpha-helix.. Residues that are generally viewed as poor helix formers in aqueous solution (e.g., Gly, ne, Val) do riot destabi lize helices, if located within a helix that spans a lipid bilayer. However , helix/bilayer mismatch such that a helix ends abruptly within the bilayer core destabilizes the end of the helix, Especially in the presence of Gly and Aln residues. Hydrogen bonding of polar side-chains with the peptide ba ckbone and with one another occurs when such residues are present within th e bilayer core, thus minimizing the energetic cost of burying such side-cha ins. (C) 2000 John Wiley & Sons, Inc.