Dynamics of the transmembrane domain of the ErbB-2 receptor

The structure and dynamics of the ErbB-2 transmembrane domain have been examined using molecular dynamics techniques both in vacuum and within an explicit hydrated L-α-dilauroyl-phosphatidyl-ethanolamine environment. In-vacuum simulations show that a highly cooperative structural transition occurs frequently within the α-helical transmembrane domain which converts to local π-helices. We show that the α-helix alteration does not depend upon the force field or initial side-chain conformations but is intimately related to the sequence. The membrane-like environment does not prevent the structural transition in the helix but slows down the peptide dynamics indicating that the appearance of a π-bulge is not an artifact of the vacuum approximation. The consequences of π-helix formation could be very huge for the ErbB-2 receptor which is involved in numerous human cancers and also for other membrane proteins wherein similar local structures are also observed experimentally.