Atomic Detail Peptide-Membrane Interactions: Molecular Dynamics Simulation of Gramicidin S in a DMPC Bilayer

AbstractMolecular dynamics simulations have been performed of the sequence-symmetric cyclic decapeptide antibiotic gramicidin S (GS), in interaction with a hydrated dimyristoylphosphatidylcholine (DMPC) bilayer, and the results compared with a “control” simulation of the system in the absence of GS. Following experimental evidence, the GS was initially set in a single antiparallel β-sheet conformation with two Type II′β-turns in an amphiphilic interaction with the membrane. This conformation and position remained in the 6.5ns simulation. Main-chain dihedrals are on average ∼26° from those determined by NMR experiment on GS in dimethylsulfoxide (DMSO) solution. Sequence-symmetric main-chain and side-chain dihedral angle pairs converge to within ∼5° and ∼10°, respectively. The area per lipid, lipid tail order parameters, and quadrupole spin-lattice relaxation times of the control simulation are mostly in good agreement with corresponding experiments. The GS has little effect on the membrane dipole potential or water permeability. However, it is found to have a disordering effect (in agreement with experiment) and a fluidifying effect on lipids directly interacting with it, and an ordering effect on those not directly interacting