Invariance of single-file water mobility in gramicidin-like peptidic pores as function of pore length.
We investigated the structural and energetic determinants underlying water permeation through peptidic nanopores, motivated by recent experimental findings that indicate that water mobility in single-file water channels displays nonlinear length dependence. To address the molecular mechanism determining the observed length dependence, we studied water permeability in a series of designed gramicidin-like channels of different length using atomistic molecular dynamics simulations. We found that within the studied range of length the osmotic water permeability is independent of pore length. This result is at variance with textbook models, where the relationship is assumed to be linear. Energetic analysis shows that loss of solvation rather than specific water binding sites in the pore form the main energetic barrier for water permeation, consistent with our dynamics results. For this situation, we propose a modified expression for osmotic permeability that fully takes into account water motion collectivity and does not depend on the pore length. Different schematic barrier profiles are discussed that explain both experimental and computational interpretations, and we propose a set of experiments aimed at validation of the presented results. Implications of the results for the design of peptidic channels with desired permeation characteristics are discussed.
Portella
Guillem
G
Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Pohl
Peter
P
de Groot
Bert L
BL
D006096:Gramicidin / Q000737:chemistry* / Q000378:metabolism*; D014867:Water / Q000378:metabolism*
D014867:Water; D006096:Gramicidin