Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The microscopic properties of water in narrow pores are relevant to the function of ion channels and related membrane transport proteins. The emergence of several high-resolution structures allows one to perform molecular dynamics simulation studies of water in such pores. Simulations of bundles of parallel alpha-helical peptides (e.g. alamethicin) have enabled development of methodologies and concepts appropriate to such investigations. In the narrow channels formed by such bundles, water molecules exhibit reduced rotational and translation motion. This reduction in water mobility may be a general property of narrow pores. We have used simplified channel models to explore the role of hydrophobicity/hydrophilicity in the entry of water into pores. Narrow pores with a hydrophobic lining, although physically open, may not admit water molecules, acting as a 'hydrophobic gate' that prevents water and ion permeation. Such a gate can be opened either by widening the pore or making its lining more polar. Simulations have been used to explore the behaviour of water in GlpF, a member of the aquaporin family of water pores, and OmpA, a bacterial outer membrane protein. Preliminary results suggest that a continuous water wire is not formed within the amphipathic GlpF pore. Simulations of OmpA, in which polar residues line the channel, indicate that a small conformational change in one of the channel lining side chains may open the channel. In summary, comparison of the behaviour of water in different narrow transmembrane pores suggests that an amphipathic pore is ideal for water permeation, and that either a highly hydrophobic pore lining or a charged pore-lining region can act as a gate.

Type

Journal article

Journal

Novartis Found Symp

Publication Date

2002

Volume

245

Pages

66 - 78

Keywords

Computer Simulation, Ion Channels, Lipid Bilayers, Models, Molecular, Protein Structure, Secondary, Water