Prediction Of Membrane Protein Orientation In Lipid Bilayers: A Theoretical Approach

Over the past few years, several three-dimensional (3-D) structures of membrane
proteins have been described with increasing accuracy, but their relationship
with membranes are still not well understood. Recently, we have developed an
empirical method, Integral Membrane Protein and Lipid Association (IMPALA), to
predict the insertion of molecules (lipids, drugs) into lipid bilayers (Proteins
30 (1998) 357). The IMPALA uses a Monte Carlo minimisation procedure to calculate
the depth and the angle of insertion of membrane-interacting molecules taking
into account the restraints dictated by a lipid bilayer. In this paper, we use
IMPALA to test the insertion of 23 integral membranous proteins (IMPs) and 2
soluble proteins into membranes. Four IMP are studied in detail: OmpA,
maltoporin, MsCl channel and bacteriorhodopsin. The 3-D structures of the
proteins are kept constant and the insertion into membrane is monitored by
minimising the value of the restraint representing the sum of two terms, one for
lipid perturbation and the other for hydrophobicity. The two soluble proteins are
rejected from the membrane whereas, under the same conditions, all the membrane
proteins remain inside, if the solvent accessible surface of the amino acids
located inside the pore of porins is ignored. The results give the tilt angle of
the IMP helices or strands with respect to the membrane surface and the depth of
the protein mass centre insertion. We conclude that the restraint terms of IMPALA
could be used to study the insertion of model structures or complexes of proteins
within membranes.