Ion-water and ion-polypeptide correlations in a gramicidin-like channel. A molecular dynamics study

This work describes a molecular dynamics study of ion-water and ion-polypeptide correlation in a model gramicidin-like channel (the polyglycine analogue) based upon interaction between polarizable, multipolar groups. The model suggests that the vicinity of the dimer junction and of the ethanolamine tail are regions of unusual flexibility. Cs+ binds weakly in the mouth of the channel: there it coordinates five water molecules and the #11CO group with which it interacts strongly and is ideally aligned. In the channel interior it is generally pentacoordinate; at the dimer junction, because of increased channel flexibility, it again becomes essentially hexacoordinate. The ion is also strongly coupled to the #13 CO but not to either #9 or #15, consistent with 13C NMR data. Water in the channel interior is strikingly different from bulk water; it has a much lower mean dipole moment. This correlates with our observation (which differs from that of previous studies) that water-water angular correlations do not persist within the channel, a result independent of ion occupancy or ionic polarity. In agreement with streaming potential measurements, there are seven single file water molecules associated with Cs+ permeation; one of these is always in direct contact with bulk water. At the mouth of an ion-free channel, there is a pattern of dipole moment alteration among the polar groups. Due to differential interaction with water, exo-carbonyls have unusually large dipole moments whereas those of the endo-carbonyls are low. The computed potential of mean force for CS+ translocation is qualitatively reasonable. However, it only exhibits a weakly articulated binding site and it does not quantitatively account for channel energetics. Correction for membrane polarization reduces, but does not eliminate, these problems.