Orientation and conformational preference of leucine-enkephalin at the surface of a hydrated dimyristoylphosphatidylcholine bilayer: NMR and MD simulation.
The morphogenic opiate pentapeptide leucine-enkephalin (lenk) in a hydrated dimyristoylphosphatidylcholine (DMPC) bilayer is studied using NMR spectroscopy and molecular dynamics simulation. Contrary to the frequent assumption that the peptide attains a single fixed conformation in the presence of membranes, we find that the lenk molecule is flexible, switching between specific bent conformations. The constraints to the orientation of the aromatic rings that are identified by the NMR experiment are found by the MD simulation to be related to the depth of the peptide in the bilayer. The motion of the N-H vectors of the peptide bonds with respect to the magnetic field direction as observed by MD largely explain the magnitude of the observed residual dipolar coupling (RDC), which are much reduced over the static (15)N-(1)H coupling. The measured RDCs are nevertheless significantly larger than the predicted ones, possibly due the absence of long-time motions in the simulations. The conformational behavior of lenk at the DMPC surface is compared to that in the aqueous solution, both in the neutral and in the zwitterionic forms.
Chandrasekhar
Indira
I
Laboratory of Physical Chemistry, ETH Zurich, 8093 Zurich, Switzerland. indira@igc.phys.chem.ethz.ch
van Gunsteren
Wilfred F
WF
Zandomeneghi
Giorgia
G
Williamson
Philip T F
PT
Meier
Beat H
BH
D003198:Computer Simulation; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D004743:Enkephalin, Leucine / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D008051:Lipid Bilayers; D014867:Water; D004743:Enkephalin, Leucine; D004134:Dimyristoylphosphatidylcholine