Abstract
The forces contributing to the association of transmembrane helices in folded membrane proteins have received considerable attention recently. In this study we investigate the importance of hydrogen bonding by studying the effect of a single Asn residue in the center of an otherwise hydrophobic transmembrane peptide using computer simulations. We use the model peptide MS1 which has been derived from the leucine zipper coiled-coil dimer of the transcription factor peptide GCN4-P1. We follow the trajectory of 36 initially monomeric MS1 transmembrane helical peptides in a membrane-mimicking octane layer as they associate into larger structures. These peptides predominately form dimers. The interaction between the polar asparagine residues, capable of simultaneously being a hydrogen-bond donor and acceptor, contributes strongly to the stability of associated helices. Only dimers with interhelical hydrogen bonds form stable structures, whereas aggregates without any hydrogen-bonding interactions form very transient structures. We examine the hydrogen-bonding patterns and find that there are two forms of dimer, one with symmetric hydrogen bonds and one with asymmetric hydrogen bonds. Based on the structures in our simulation we propose a model with a monomer <--> symmetric dimer <--> asymmetric dimer <--> trimer equilibrium.