Insertion and hairpin formation of membrane proteins: a Monte Carlo study.

Some particular effects of a lipid membrane on the partitioning and the concomitant folding processes of model proteins have been investigated using Monte Carlo methods. It is observed that orientational order and lateral density fluctuations of the lipid matrix stabilize the orientation of helical proteins and induce a tendency of spontaneous formation of helical hairpins for helices longer than the width of the membrane. The lateral compression of the lipids on a hairpin leads to the extrusion of a loop at the trans side of the membrane. The stability of the hairpin can be increased by the design of appropriate groups of hydrophilic and hydrophobic residues at the extruded loop. It is shown that in the absence of lipids the orientation of proteins is not stable and the formation of hairpins is absent. Some analogies between the formation of helical hairpins in membranes and the formation of hairpins in polymer liquid crystals are discussed. The simulations indicate that the insertion process follows a well-defined pattern of kinetic steps.