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Free‐energy profiles for ions in the influenza M 2 ‐TMD channel
Author(s) -
Mustafa Morad,
Henderson Douglas J.,
Busath David D.
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22376
Subject(s) - chemistry , tetramer , molecular dynamics , umbrella sampling , selectivity , ion , permeation , lipid bilayer , membrane , bilayer , analytical chemistry (journal) , crystallography , computational chemistry , chromatography , organic chemistry , biochemistry , enzyme , catalysis
M 2 transmembrane domain channel (M 2 ‐TMD) permeation properties are studied using molecular dynamics simulations of M 2 ‐TMD (1NYJ) embedded in a lipid bilayer (DMPC) with 1 mol/kg NaCl or KCl saline solution. This study allows examination of spontaneous cation and anion entry into the selectivity filter. Three titration states of the M 2 ‐TMD tetramer are modeled for which the four His 37 residues, forming the selectivity filter, are net uncharged, +2 charged, or +3 charged. M 2 ‐TMD structural properties from our simulations are compared with the properties of other models extracted from NMR and X‐ray studies. During 10 ns simulations, chloride ions occasionally occupy the positively‐charged selectivity filter region, and from umbrella sampling simulations, Cl − has a lower free‐energy barrier in the selectivity‐filter region than either Na + or NH 4 + , and NH 4 +has a lower free‐energy barrier than Na + . For Na + and Cl − , the free‐energy barriers are less than 5 kcal/mol, suggesting that the 1NYJ conformation would probably not be exquisitely proton selective. We also point out a rotameric configuration of Trp 41 that could fully occlude the channel. Proteins 2009. © 2009 Wiley‐Liss, Inc.