Water in Nanopores and Biological Channels: A Molecular Simulation Perspective

Abstract

This Review explores the dynamic behavior of water within nanopores and biological channels in lipid bilayer membranes. We focus on molecular simulation studies, alongside selected structural and other experimental investigations. Structures of biological nanopores and channels are reviewed, emphasizing those high-resolution crystal structures, which reveal water molecules within the transmembrane pores, which can be used to aid the interpretation of simulation studies. Different levels of molecular simulations of water within nanopores are described, with a focus on molecular dynamics (MD). In particular, models of water for MD simulations are discussed in detail to provide an evaluation of their use in simulations of water in nanopores. Simulation studies of the behavior of water in idealized models of nanopores have revealed aspects of the organization and dynamics of nanoconfined water, including wetting/dewetting in narrow hydrophobic nanopores. A survey of simulation studies in a range of nonbiological nanopores is presented, including carbon nanotubes, synthetic nanopores, model peptide nanopores, track-etched nanopores in polymer membranes, and hydroxylated and functionalized nanoporous silica. These reveal a complex relationship between pore size/geometry, the nature of the pore lining, and rates of water transport. Wider nanopores with hydrophobic linings favor water flow whereas narrower hydrophobic pores may show dewetting. Simulation studies over the past decade of the behavior of water in a range of biological nanopores are described, including porins and β-barrel protein nanopores, aquaporins and related polar solute pores, and a number of different classes of ion channels. Water is shown to play a key role in proton transport in biological channels and in hydrophobic gating of ion channels. An overall picture emerges, whereby the behavior of water in a nanopore may be predicted as a function of its hydrophobicity and radius. This informs our understanding of the functions of diverse channel structures and will aid the design of novel nanopores. Thus, our current level of understanding allows for the design of a nanopore which promotes wetting over dewetting or vice versa. However, to design a novel nanopore, which enables fast, selective, and gated flow of water de novo would remain challenging, suggesting a need for further detailed simulations alongside experimental evaluation of more complex nanopore systems.

Artificial Water Channels: Towards Biomimetic Membranes for Desalination

“…Their pores are completely filled with water molecules. Molecular simulations show that water diffuses more slowly than in bulk, probably owing to the strong structuration of water within the pores, similar to what is observed in carbon nanotubes (CTNs) [7e] …”

Molecular dynamics simulations reveal statistics and microscopic mechanisms of water permeation in membrane-embedded artificial water channel nanoconstructs

“…However these structural changes of water have to be challenged under non-equilibrium conditions such as electrical fields, osmotic and hydrostatic pressure [32][33][34] . A coarse-grain approach 35,36 applied to the specific treatment of synthetic materials would be necessary to access significantly longer timescales and to probe scalability for the future applications in inverse osmosis and ultrafiltration devices 37,38 . FIG.…”

Transmembrane Self-Assembled Cyclic Peptide Nanotubes Based on α‐Residues and Cyclic δ‐Amino Acids: A Computational Study

“…Since experimental measurement about confined molecule properties in the nanoscale is difficult ( Rodríguez-Vázquez et al, 2017 ), molecular dynamics (MD) simulations play a key role in the description of these systems ( Lynch et al, 2020 ). Recent studies carried out in our group showed that α,δ-SCPNs are stable and theoretically able to translocate water and cations when inserted into a lipid bilayer ( Calvelo et al, 2021 ).…”