Do interhelical side chain-backbone hydrogen bonds participate in formation of leucine zipper coiled coils?

The leucine zipper proteins are a group of transcriptional regulators that dimerize to form a DNA binding domain. It has been proposed that this dimerization results from the hydrophobic association of the alpha-helices of two leucine zipper monomers into a coiled coil. We propose a model for a coiled coil based on a periodic hydrophobic-hydrophilic amino acid motif found in the leucine zipper regions of 11 transcriptional regulatory proteins. This model predicts the symmetrical formation of secondary hydrogen bonds between the polar side chains of one helix and the peptide carbonyls of the opposite chain, supplementing the interactions between hydrophobic side chains. Physical modeling (CPK) and in vacuo molecular mechanics calculations of the stability of the GCN4 leucine zipper coiled coil configured in accordance with this model demonstrate a greater stability for this conformer than for a conformer configured according to a current hydrophobic model. Molecular dynamics simulations show similar stability of the two models in vacuo but a higher stability of the hydrophobic model in water.