%0 Journal Article %1 Nguyen20131569 %A Nguyen, Thuy Hien T. %A Liu, Zhiwei %A Moore, Preston B. %D 2013 %J Biophysical Journal %K imported %N 7 %P 1569 - 1580 %R http://dx.doi.org/10.1016/j.bpj.2013.07.053 %T Molecular Dynamics Simulations of Homo-oligomeric Bundles Embedded Within a Lipid Bilayer %U http://www.sciencedirect.com/science/article/pii/S0006349513008795 %V 105 %X Abstract Using molecular dynamics simulations, we studied the structure, interhelix interactions, and dynamics of transmembrane proteins. Specifically, we investigated homooligomeric helical bundle systems consisting of synthetic α-helices with either the sequence Ac-(LSLLLSL)3-NH2 (LS2) or Ac-(LSSLLSL)3-NH2 (LS3). The ŁS2\ and ŁS3\ helical peptides are designed to have amphipathic characteristics that form ion channels in membrane. We simulated bundles containing one to six peptides that were embedded in palmitoyl-oleoyl-phosphatidylcholine (POPC) lipid bilayer and placed between two lamellae of water. We aim to provide a fundamental understanding of how amphipathic helical peptides interact with each other and their dynamical behaviors in different homooligomeric states. To understand structural properties, we examined the helix lengths, tilt angles of individual helices and the entire bundle, interhelix distances, interhelix cross-angles, helix hydrophobic-to-hydrophilic vector projections, and the average number of interhelix hydrophilic (serine–serine) contacts lining the pore of the transmembrane channel. To analyze dynamical properties, we calculated the rotational autocorrelation function of each helix and the cross-correlation of the rotational velocity between adjacent helices. The observed structural and dynamical characteristics show that higher order bundles containing four to six peptides are composed of multiple lower order bundles of one to three peptides. For example, the ŁS2\ channel was found to be stable in a tetrameric bundle composed of a “dimer of dimers.” In addition, we observed that there is a minimum of two strong hydrophilic contacts between a pair of adjacent helices in the dimer to tetramer systems and only one strong hydrophilic interhelix contact in helix pairs of the pentamer and hexamer systems. We believe these results are general and can be applied to more complex ion channels, providing insight into ion channel stability and assembly.

@article{Nguyen20131569, abstract = {Abstract Using molecular dynamics simulations, we studied the structure, interhelix interactions, and dynamics of transmembrane proteins. Specifically, we investigated homooligomeric helical bundle systems consisting of synthetic α-helices with either the sequence Ac-(LSLLLSL)3-NH2 (LS2) or Ac-(LSSLLSL)3-NH2 (LS3). The \{LS2\} and \{LS3\} helical peptides are designed to have amphipathic characteristics that form ion channels in membrane. We simulated bundles containing one to six peptides that were embedded in palmitoyl-oleoyl-phosphatidylcholine (POPC) lipid bilayer and placed between two lamellae of water. We aim to provide a fundamental understanding of how amphipathic helical peptides interact with each other and their dynamical behaviors in different homooligomeric states. To understand structural properties, we examined the helix lengths, tilt angles of individual helices and the entire bundle, interhelix distances, interhelix cross-angles, helix hydrophobic-to-hydrophilic vector projections, and the average number of interhelix hydrophilic (serine–serine) contacts lining the pore of the transmembrane channel. To analyze dynamical properties, we calculated the rotational autocorrelation function of each helix and the cross-correlation of the rotational velocity between adjacent helices. The observed structural and dynamical characteristics show that higher order bundles containing four to six peptides are composed of multiple lower order bundles of one to three peptides. For example, the \{LS2\} channel was found to be stable in a tetrameric bundle composed of a “dimer of dimers.” In addition, we observed that there is a minimum of two strong hydrophilic contacts between a pair of adjacent helices in the dimer to tetramer systems and only one strong hydrophilic interhelix contact in helix pairs of the pentamer and hexamer systems. We believe these results are general and can be applied to more complex ion channels, providing insight into ion channel stability and assembly. }, added-at = {2016-05-13T19:16:40.000+0200}, author = {Nguyen, Thuy Hien T. and Liu, Zhiwei and Moore, Preston B.}, biburl = {https://www.bibsonomy.org/bibtex/29c9c25ead0fdbd9b0b21a6a7e5d2b7fb/templehpc}, description = {Molecular Dynamics Simulations of Homo-oligomeric Bundles Embedded Within a Lipid Bilayer}, doi = {http://dx.doi.org/10.1016/j.bpj.2013.07.053}, interhash = {c9832f504021f19e8a0912586f069472}, intrahash = {9c9c25ead0fdbd9b0b21a6a7e5d2b7fb}, issn = {0006-3495}, journal = {Biophysical Journal }, keywords = {imported}, number = 7, pages = {1569 - 1580}, timestamp = {2016-05-13T19:17:46.000+0200}, title = {Molecular Dynamics Simulations of Homo-oligomeric Bundles Embedded Within a Lipid Bilayer }, url = {http://www.sciencedirect.com/science/article/pii/S0006349513008795}, volume = 105, year = 2013 }