Characterizing Residue-Bilayer Interactions Using Gramicidin A as a Scaffold and Tryptophan Substitutions as Probes

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Issue Date
2017-10-10Author
Beaven, Andrew H.
Sodt, Alexander J.
Pastor, Richard W.
Koeppe, Roger E., II
Andersen, Olaf S.
Im, Wonpil
Publisher
American Chemical Society
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
© American Chemical Society
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Show full item recordAbstract
Previous experiments have shown that the lifetime of a gramicidin A dimer channel (which forms from two non-conducting monomers) in a lipid bilayer is modulated by mutations of the tryptophan (Trp) residues at the bilayer-water interface. We explore this further using extensive molecular dynamics simulations of various gA dimer and monomer mutants at the Trp positions in phosphatidylcholine bilayers with different tail lengths. gA interactions with the surrounding bilayer are strongly modulated by mutating these Trp residues. There are three principal effects: eliminating residue hydrogen bonding ability (i.e., reducing the channel-monolayer coupling strength) reduces the extent of the bilayer deformation caused by the assembled dimeric channel; a residue’s size and geometry affects its orientation, leading to different hydrogen bonding partners; and increasing a residue’s hydrophobicity increases the depth of gA monomer insertion relative to the bilayer center, thereby increasing the lipid bending frustration.
Description
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Theory and Computation, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/acs.jctc.7b00400.
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Citation
Beaven, A. H., Sodt, A. J., Pastor, R. W., Koeppe, R. E., Andersen, O. S., & Im, W. (2017). Characterizing Residue-Bilayer Interactions Using Gramicidin A as a Scaffold and Tryptophan Substitutions as Probes. Journal of chemical theory and computation, 13(10), 5054-5064.
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