GxxxG motif stabilize ion-channel like pores through C?-H???OH interaction in a?(1-40)

A (1-40) can transfer from the aqueous phase to the bilayer and thus form stable ionchannel-
like pores where the protein has alpha-helical conformation. The stability of the pores is
due to the presence of the GXXXG motif. It has been reported that these ion-channel-like pores
are stabilized by a C–HO hydrogen bond that is established between a glycine of the GXXXG
sequence of an alpha-helix and another amino acid of a vicinal alpha-helix. However, conflicting
data are reported in the literature. Some authors have suggested that hydrogen bonding does
not have a stabilizing function. Here we synthesized pentapeptides having a GXXXG motif to
explore its role in pore stability. We used molecular dynamics simulations, quantum mechanics, and
experimental biophysical techniques to determine whether hydrogen bonding was formed and had a
stabilizing function in ion-channel-like structures. Starting from our previous molecular dynamics
data, molecular quantum mechanics simulations, and ATR data showed that a stable ion-channel-like
pore formed and a band centered at 2910 cm?1 was attributed to the interaction between Gly 7 of an
alpha-helix and Asp 23 of a vicinal alpha-helix