DETAILED DESCRIPTION OF AN ALPHA-HELIX-]PI BULGE TRANSITION DETECTED BY MOLECULAR-DYNAMICS SIMULATIONS OF THE P185(C-ERBB2) V659G TRANSMEMBRANE DOMAIN

Molecular dynamics simulations of a 29-residue peptide including the t ransmembrane domain of the V659G mutant of the c-erbB2 protein demonst rate important dynamical behavior. Although the alpha helix is the str ucture commonly assumed for transmembrane hydrophobic segments, we fou nd that hydrogen bond rearrangements can occur, giving rise to a struc tural deformation termed pi bulge stabilized by successive hydrogen bo nds of pi helix type. A series of simulations enables us to give a det ailed description, at the atomic level, of the alpha helix-->pi bulge transition. The major consequence of this deformation covering one and a half rum of helix results in a noticeable shift around the helix ax is of the C-terminal residues relatively to those of the N-terminus. S uch a deformation closely related to structural motifs described in th e litterature, induces a change in the distribution of the residues al ong the helix faces which could modulate the protein activity mediated by a dimerization process.