Dynamics of lipids, cholesterol, and transmembrane α-helices from microsecond molecular dynamics simulations.
Extensive all-atom molecular dynamics (∼24 μs total) allowed exploration of configurational space and calculation of lateral diffusion coefficients of the components of a protein-embedded, cholesterol-containing model bilayer. The three model membranes are composed of an ∼50/50 (by mole) dipalmitoylphosphatidylcholine (DPPC)/cholesterol bilayer and contained an α-helical transmembrane protein (HIV-1 gp41 TM). Despite the high concentration of cholesterol, normal Brownian motion was observed and the calculated diffusion coefficients (on the order of 10(-9) cm(2)/s) are consistent with experiments. Diffusion is sensitive to a variety of parameters, and a temperature difference of ∼4 K from thermostat artifacts resulted in 2-10-fold differences in diffusion coefficients and significant differences in lipid order, membrane thickness, and unit cell area. Also, the specific peptide sequence likely underlies the consistently observed faster diffusion in one leaflet. Although the simulations here present molecular dynamics (MD) an order of magnitude longer than those from previous studies, the three systems did not approach ergodicity. The distributions of cholesterol and DPPC around the peptides changed on the microsecond time scale, but not significantly enough to thoroughly explore configurational space. These simulations support conclusions of other recent microsecond MD in that even longer time scales are needed for equilibration of model membranes and simulations of more realistic cellular or viral bilayers.
Department of Chemical and Biological Engineering, Drexel University , 3141 Chestnut Street, Philadelphia, Pennsylvania 19104, United States.
Michelle K
MK
Baker
Cameron F
CF
Abrams
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D004058:Diffusion; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary; D013696:Temperature; D014867:Water / Q000737:chemistry
D015700:HIV Envelope Protein gp41; D008051:Lipid Bilayers; D008055:Lipids; C514787:gp41 protein, Human immunodeficiency virus 1; D014867:Water; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol