title: Ion channel stability of Gramicidin A in lipid bilayers: effect of hydrophobic mismatch.
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.
authors.affiliation: Department of Chemistry, University of Calcutta, 92, A. P. C. Road, Kolkata 700009, India.
authors.forename: Ipsita
authors.initials: I
authors.lastname: Basu
authors.forename: Amitabha
authors.initials: A
authors.lastname: Chattopadhyay
authors.forename: Chaitali
authors.initials: C
authors.lastname: Mukhopadhyay
mesh_terms: D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D006096:Gramicidin / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007473:Ion Channels / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D006096:Gramicidin; C044819:1,2-diarachidonoyl-glycero-3-phosphocholine; C002448:1,2-linoleoylphosphatidylcholine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; D004134:Dimyristoylphosphatidylcholine
keywords: DAPC bilayer; Gramicidin A; Ion channel stability; Negative hydrophobic mismatch