Nearly a quarter of genomic sequences and almost half of all receptors that
are likely to be targets for drug design are integral membrane proteins.
Understanding the detailed mechanisms of the folding of membrane proteins is a
largely unsolved, key problem in structural biology. Here, we introduce a
general model and use computer simulations to study the equilibrium properties
and the folding kinetics of a Cα-based two helix bundle fragment
(comprised of 66 amino-acids) of Bacteriorhodopsin. Various intermediates are
identified and their free energy are calculated toghether with the free energy
barrier between them. In 40% of folding trajectories, the folding rate is
considerably increased by the presence of non-obligatory intermediates acting
as traps. In all cases, a substantial portion of the helices is rapidly formed.
This initial stage is followed by a long period of consolidation of the helices
accompanied by their correct packing within the membrane. Our results provide
the framework for understanding the variety of folding pathways of helical
transmembrane proteins