Lattice model of transmembrane polypeptide folding

Folding of hydrophobic polypeptides into unique three-dimensional structures in a membrane is investigated by Monte Carlo simulations using the bond fluctuation model. Its ground stale structure can be a helix or a double helix depending on the competition of hydrogen bonding and backbone bending energies. The folding pathway of hydrophobic polypeptides in a nonpolar environment is found to favor the helical structure over the double helix. The folding time of a transmembrane domain increases exponentially with the chain length. Folding at low temperatures exhibits an Arrhenius-like behavior. We discuss the kinetics of both random folding and channel complex assisted folding of a polypeptide chain. Our results suggest a significantly smaller energetic barrier in the folding pathway for channel complex assisted folding.