MD simulations of spontaneous membrane protein/detergent micelle formation

The in vitro study of membrane proteins for the purpose of physicochemical analysis or structure determination often relies upon successful reconstitution into detergent micelles. Moreover, a number of biological processes such as membrane protein folding and transport rely on lipid interactions which may resemble the micellar environment. Little is known about the structures of these micelles or the processes which lead to their formation. We therefore present two 50 ns all-atom molecular dynamics simulations of spontaneous dodecylphosphocholine micelle formation around representatives of the two major families of membrane proteins, a small β-barrel protein, OmpA, and a model α-helical protein, glycophorin A. Despite differences in protein architecture, we highlight common mechanistic pathways in micelle formation, which are consistent with experimental studies. We characterize the exponential kinetics of detergent-protein adsorption and suggest a simple model which may explain the aggregation process. We also compare the results with 25 and 50 ns simulations of preformed micelles containing the same proteins. We confirm that the end structures of the self-assembled micelles are similar to those from their preformed counterparts, with each micelle presenting a bilayerlike environment to the enclosed protein. Copyright © 2004 American Chemical Society.