alpha-Helix dipole model and electrostatic stabilization of 4-alpha-helical proteins.

Abstract

A simple dipole model is developed for estimation of the electrostatic interaction energy between .alpha.-helices in proteins. This model is used to estimate the electrostatic stabilization in a recurrent protein tertiary structural motif, an array of 4 closely packed .alpha.-helices. For the proteins examined (cytochrome c'', hemerythrin, myohemerythrin, cytochrome b562, and a T4 phage lysozyme domain), their common antiparallel arrangement of adjacent helices confers a stabilization of 5-7 kcal/mol (1 cal = 4.18 J). In contrast, a similarly packed array of parallel helices is relatively destabilized by 20 kcal/mol. Helix-dipole interactions are important in the stabilization of this structural motif. These effects are discussed both in the context of folding pathways for 4-.alpha.-helical proteins and the stabilization of the higher aggregates.