Determinants of water and ion permeation through nanopores studied by Molecular Dynamics simulations

Abstract

Membrane channels facilitate the transport of matter through the cell membrane, and therefore play a crucial role in life. The knowledge of the structure-permeability relationships in model channels is essential for the understanding of natural membrane channels and for the design of novel channels with desired characteristics. The aim of this thesis is towards the characterization of the critical fundamental factors that determine water and ion permeation through channels of molecular dimensions. To this end, we performed atomistic molecular dynamics simulations to extract crucial energetic and dynamic properties underlying water and ion permeation in nanopores with different geometries and polarities. First, we show that a systematic approach where only one property is varied at the time is required. We then use a series of designed peptidic channels that permeate water in single-file regime to isolate the influence of the channel length on the water mobility. The extension of the channel is found to have no impact on the water mobility. In contrast, we show that the polarity of the channels strongly influences the water permeability, ranging from almost empty pores to tightly adsorbed water molecules. The channel polarity corresponding to the natural peptidic channels is found to be close to optimal for water permeation. The water mobility within a given water-pore affinity remains invariant with the length. Moreover, by systematically varying the radius and the polarity of model pores, we find a strong effect of the pore radius and polarity on the water pore occupancy and water permeability over a range of radii of 0.4 nm. Water permeabilities span two orders of magnitude as the pore radius increases, approaching the macroscopic radial dependence at large radii. Finally, we show that free energy barriers for ion permeation through single-file pores display a strong length dependence. A central barrier emerges until saturation as the channels elongates, correlating with desolvation of the ion from the bulk. Whereas the main contribution to the ion permeation free energy barrier is found to be entropic, the length dependence of the permeation barrier is dictated by the enthalpic contribution. Implications of the presented results for the understanding of natural channels and for the design of novel channels are discussed throughout this thesis.