THE M2 CHANNEL OF INFLUENZA-A VIRUS - A MOLECULAR-DYNAMICS STUDY

Molecular dynamics simulations have been performed on a tetramer of th e 25-residue (SSDPLVVAASIIGILHLILWILDRL) synthetic peptide [1] which c ontains the transmembrane domain of the influenza A virus M2 coat prot ein. The peptide bundle was initially assembled as a parallel alpha-he lix bundle in the octane portion of a phase separated water/octane sys tem, which provided a membrane-mimetic environment, A 4-ns dynamics tr ajectory identified a left-handed coiled coil state of the neutral bun dle, with a water filled funnel-like structural motif at the N-terminu s involving the long hydrophobic sequence. The neck of the funnel begi ns at V27 and terminates at H37, which blocks the channel. The C-termi nus is held together by inter-helix hydrogen bonds and contains water below H37, Solvation of the S23 and D24 residues, located at the rim o f the funnel, appears to be important for stability of the structure. The calculated average tilt of the helices in the neutral bundle is 27 +/- 5 degrees, which agrees well with recent NMR data. (C) 1998 Feder ation of European Biochemical Societies.