Dynamics of the transmembrane domain of the ErbB-2 receptor

The structure and dynamics of the ErbB-2 transmembrane domain have been exa mined using molecular dynamics techniques both in Vacuum and within an expl icit hydrated L-alpha-dilauroyl-phosphatidyl-ethanolamine environment. In-v acuum simulations show that a highly cooperative structural transition occu rs frequently within the alpha-helical transmembrane domain which converts to local pi-helices. We show that the alpha-helix alteration does not depen d upon the force held or initial side-chain conformations but is intimately related to the sequence. The membrane-like environment does not prevent th e structural transition in the helix but slows down the peptide dynamics in dicating that the appearance of a pi-bulge is not an artifact of the Vacuum approximation. The consequences of pi-helix formation could be very huge f or the ErbB-2 receptor which is involved in numerous human cancers and also for other membrane proteins wherein similar local structures are also obse rved experimentally.