Ion channel stability and hydrogen bonding molecular modelling of channels formed by synthetic alamethicin analogues

Journal article

Several analogues of the channel-forming peptaibol alamethicin have been demonstrated to exhibit faster switching between channel substates than does unmodified alamethicin. Molecular modelling studies are used to explore the possible molecular basis of these differences. Models of channels formed by alamethicin analogues were generated by restrained molecular dynamics in vacuo and refined by short molecular dynamics simulations with water molecules within and at either mouth of the channel. A decrease in backbone solvation was found to correlate with a decrease in open channel stability between alamethicin and an analogue in which all α-amino-isobutyric acid residues of alamethicin were replaced by leucine. A decrease in the extent of hydrogen-bonding at residue 7 correlates with lower open channel stabilities of analogues in which the glutamine at position 7 was replaced by smaller polar sidechains. These two observations indicate the importance of alamethicin/water H-bonds in stabilizing the open channel.

Authors: Breed, J; Kerr, I; Molle, G; Duclohier, H; Sansom, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes
• Volume: 1330
• Issue: 2
• Pages: 103–109
• Publication date: 1997-12-01
• Edition: Publisher's version
• DOI: 10.1016/S0005-2736(97)00163-6
• ISSN: 0006-291X
• Language: English
• Keywords: Alamethicin; Channel-forming peptide; Peptaibol; Molecular dynamics; Ion channel