BIOPHYSICAL THEORY AND MODELING |
Molecular Dynamics Simulation of Transmembrane
Polypeptide Orientational Fluctuations
David J. Goodyear 1, Simon Sharpe 2, Chris W. M. Grant 2 and Michael R. Morrow 1*
1 Memorial University of Newfoundland
2 University of Western Ontario
* To whom correspondence should be addressed. E-mail: myke{at}physics.mun.ca.
Submitted on June 21, 2004
Revised on July 21, 2004
Accepted on 12 October 2004
 |
Abstract |
|---|
The orientation and motion of a model lysine-terminated transmembrane polypeptide were investigated by Molecular Dynamics simulation. Recent 2H NMR studies of synthetic polypeptides with deuterated alanine sidechains suggest that such transmembrane polypeptides undergo fast, axially symmetric reorientation about the bilayer normal but have a preferred average azimuthal orientation about the helix axis. In the present work, interactions that might contribute to this behavior were investigated in a simulated system consisting of 64 molecules of 1-palmitoyl-2-oleoyl-sn glycero-3-phosphocholine (POPC) and one á-helical polypeptide with the sequence acetyl-KK-(LA)11-KK amide. In one simulation, initiated with the peptide oriented along the bilayer normal, the system was allowed to evolve for 8.5 ns at 1 atmosphere of pressure and a temperature of 55°C. A second simulation was initiated with the peptide orientation chosen to match a set of experimentally-observed alanine methyl deuteron quadrupole splittings and allowed to proceed for 10 ns. Simulated alanine methyl group orientations were found to be inequivalent, a result that is consistent with 2H NMR observations of specifically-labeled polypeptides in POPC bilayers. Helix tilt varied substantially over the durations of both simulations. In the first simulation, the peptide tended toward an orientation about the helix axis similar to that suggested by experiment. In the second simulation, orientation about the helix axis tended to return to this value following an excursion. These results provide some insight into how interactions at the bilayer surface can constrain reorientation about the helix axis while accommodating large changes in helix tilt.
Key Words:
deuterium NMR, model membrane, molecular dynamics simulation, transmembrane polypeptide
