CORRELATED MOTIONS AND PROPAGATION OF THE EFFECT OF A LOCAL CONFORMATIONAL CHANGE IN THE TRANSMEMBRANE HELIX OF THE C-ERBB2 ENCODED PROTEINAND IN ITS V659E MUTANT, STUDIED BY MOLECULAR-DYNAMICS SIMULATIONS

A detailed study of the dynamical behavior of the 29-residue peptide i ncluding the transmembrane domain of p185(c-erbB2) oncogene-encoded pr otein and of its V659E mutant is presented. In a first part of this wo rk we analyse equal time correlation coefficients between the backbone dihedral angle fluctuations. Concerted motions are observed in the wi ld type transmembrane a-helix but not in the corresponding V659E intra membrane domain. The difference observed in the correlation pattern is attributed to the single amino acid replacement. In a second part, we investigate the propagation of the effect of a local conformational c hange along the transmembrane segment, one of the dominant hypotheses for signal transduction mechanisms of transmembrane receptors. The ana lysis of angular time correlation functions together with that of the response of the different residues to a local disturbance applied at t he N-terminal side evidences a propagation phenomenon for the wild typ e peptide. This effect is much less clear for the mutated peptide. Fur thermore we show that the first one is much more flexible than the sec ond one.