Molecular Dynamics Simulations of GlpF in a Micelle vs in a Bilayer: Conformational Dynamics of a Membrane Protein as a Function of Environment

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Abstract
Octyl glucoside (OG) is a detergent widely employed in structural and functional studies of membrane proteins. To better understand the nature of protein−OG interactions, molecular dynamics simulations (duration 10 ns) have been used to explore an α-helical membrane protein, GlpF, in OG micelles and in DMPC bilayers. Greater conformational drift of the extramembraneous protein loops, from the initial X-ray structure, is seen for the GlpF−OG simulations than for the GlpF−DMPC simulation. The mobility of the transmembrane α-helices is ∼1.3x higher in the GlpF−OG than the GlpF−DMPC simulations. The detergent is seen to form an irregular torus around the protein. The presence of the protein leads to a small perturbation in the behavior of the alkyl chains in the OG micelle, namely an ∼15% increase in the trans−gauche(−)-gauche(+) transition time. Aromatic side chains (Trp, Tyr) and basic side chains (Arg, Lys) play an important role in both protein−detergent (OG) and protein−lipid (DMPC) interactions.