MOLECULAR MODELING OF C-ERBB2 RECEPTOR DIMERIZATION - COILED-COIL STRUCTURE OF WILD AND ONCOGENIC TRANSMEMBRANE DOMAINS - STABILIZATION BY INTERHELICAL HYDROGEN-BONDS IN THE ONCOGENIC FORM

Dimerization models of c-erbB2 transmembrane domains (Leu651-Ile675) a re studied by molecular mechanics and molecular dynamics simulations. Both wild and Glu mutated transmembrane helices exhibit the same relat ive orientation for favorable associations and dimerize preferentially in left-handed coiled-coil structures. The mutation point 659 belongs to the interfacing residues, and in the transforming domain, symmetri c hydrogen bonds between Glu carboxylic groups stabilize the dimeric s tructure. The same helix packing found for the wild dimers, except sid e-chain-side-chain hydrogen bonds, suggests that the transmembrane dom ains dimerize according to similar process. Structural and energetical characterization of the models are presented. (C) 1997 John Wiley & S ons, Inc.