Ion channel stability of Gramicidin A in lipid bilayers: effect of hydrophobic mismatch.

Ipsita Basu, Amitabha Chattopadhyay, Chaitali Mukhopadhyay

Index: Biochim. Biophys. Acta 1838(1 Pt B) , 328-38, (2014)

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Abstract

Hydrophobic mismatch which is defined as the difference between the lipid hydrophobic thickness and the peptide hydrophobic length is known to be responsible in altering the lipid/protein dynamics. Gramicidin A (gA), a 15 residue β helical peptide which is well recognized to form ion conducting channels in lipid bilayer, may change its structure and function in a hydrophobic mismatched condition. We have performed molecular dynamics simulations of gA dimer in phospholipid bilayers to investigate whether or not the conversion from channel to non-channel form of gA dimer would occur under extreme negative hydrophobic mismatch. By varying the length of lipid bilayers from DLPC (1, 2-Dilauroyl-sn-glycero-3-phosphocholine) to DAPC (1, 2-Diarachidoyl-sn-glycero-3-phosphocholine), a broad range of mismatch was considered from nearly matching to extremely negative. Our simulations revealed that though the ion-channel conformation is retained by gA under a lesser mismatched situation, in extremely negative mismatched situation, in addition to bilayer thinning, the conformation of gA is changed and converted to a non-channel one. Our results demonstrate that although the channel conformation of Gramicidin A is the most stable structure, it is possible for gA to change its conformation from channel to non-channel depending upon the local environment of host bilayers. © 2013.