Structure and dynamics of solvent molecules inside the polytheonamide B channel in different environments: A molecular dynamics study

The β^6.3-helical channel of the marine cytotoxic peptide, polytheonamide B (pTB), is examined in water, the POPC bilayer, and a 1:1 chloroform/methanol mixture using all-atom molecular dynamics simulations. The structures and fluctuations of the β^6.3-helix of pTB are investigated in the three environments. The average structure of pTB calculated in the mixed solvent is in good agreement with the NMR-resolved structure in the mixed solvent, indicating the validity of the parameters used for the non-standard groups in pTB. The configuration and dynamics of solvent molecules inside the pore are examined in detail. It is found that the motions of methanol molecules inside the pore are not correlated because of the absence of strong hydrogen bonds (HBs) between adjacent methanol molecules. On the other hand, the motions of water molecules inside the pore are highly correlated, both translationally and orientationally, due to the strong HBs between neighboring water molecules. It is suggested that the collective behavior of water molecules inside the pore in the membrane is crucial for the permeation of ions through the pTB channel.