TRANSMEMBRANE HELIX STRUCTURE, DYNAMICS, AND INTERACTIONS - MULTI-NANOSECOND MOLECULAR-DYNAMICS SIMULATIONS

To probe the fundamentals of membrane/protein interactions, all-atom m ulti-nanosecond molecular dynamics simulations were conducted on a sin gle transmembrane poly(32)alanine helix in a fully solvated dimyristoy phosphatidylcholine (DMPC) bilayer. The central 12 residues, which int eract only with the lipid hydrocarbon chains, maintained a very stable helical structure. Helical regions extended beyond these central 12 r esidues, but interactions with the lipid fatty-acyl ester linkages, th e lipid headgroups, and water molecules made the helix less stable in this region. The C and N termini, exposed largely to water, existed as random coils. As a whole, the helix tilted substantially, from perpen dicular to the bilayer plane (0 degrees) to a 30 degrees tilt. The hel ix experienced a bend at its middle, and the two halves of the helix a t times assumed substantially different tilts. Frequent hydrogen bondi ng, of up to 0.7 ns in duration, occurred between peptide and lipid mo lecules. This resulted in correlated translational diffusion between t he helix and a few lipid molecules. Because of the large variation in lipid conformation, the lipid environment of the peptide was not well defined in terms of ''annular'' lipids and on average consisted of 18 lipid molecules. When compared with a ''neat'' bilayer without peptide , no significant difference was seen in the bilayer thickness, lipid c onformations or diffusion, or headgroup orientation. However, the lipi d hydrocarbon chain order parameters showed a significant decrease in order, especially in those methylene groups closest to the headgroup.