MOLECULAR-DYNAMICS SIMULATIONS OF ISOLATED TRANSMEMBRANE HELICES OF POTASSIUM CHANNELS

In the middle of the S6 helix in voltage-gated potassium channels ther e is a highly conserved Pro-Val-Pro motif; while the equivalent M2 hel ix of inward rectifier potassium channels contains a conserved glycine residue in a comparable position. The structural implications of thes e conserved motifs are of interest given the evidence that S6 and M2 a re components of the lining of their respective pores. Multiple sequen ce alignment and TM helix prediction methods were used to define conse nsus regions for S6 and M2. Ensembles of 50 structures for each helix were generated by simulated annealing and restrained molecular dynamic s. Time-dependent fluctuations of S6 and M2 were investigated by long time scale molecular dynamics simulations on representative members of each ensemble carried out in vacuo in the presence and absence of a h ydrophobic potential that mimics a lipid bilayer. The results are disc ussed in terms of the structural basis of the kink in S6 and M2 and of a putative functional role for flexible helices as ''molecular swivel s.'' (C) 1996 John Wiley & Sons, Inc.