Molecular dynamics study of homo-oligomeric ion channels: Structures of the surrounding lipids and dynamics of water movement
Molecular dynamics simulations were used to study the structural perturbations of lipids surrounding transmembrane ion channel forming helices/helical bundles and the movement of water within the pores of the ion-channels/bundles. Specifically, helical monomers to hexameric helical bundles embedded...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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AIMS Press
2018-03-01
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| Series: | AIMS Biophysics |
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| Online Access: | http://www.aimspress.com/biophysics/article/1868/fulltext.html |
| _version_ | 1818174607723593728 |
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| author | Thuy Hien Nguyen Catherine C. Moore Preston B. Moore Zhiwei Liu |
| author_facet | Thuy Hien Nguyen Catherine C. Moore Preston B. Moore Zhiwei Liu |
| author_sort | Thuy Hien Nguyen |
| collection | DOAJ |
| description | Molecular dynamics simulations were used to study the structural perturbations of lipids surrounding transmembrane ion channel forming helices/helical bundles and the movement of water within the pores of the ion-channels/bundles. Specifically, helical monomers to hexameric helical bundles embedded in palmitoyl-oleoyl-phosphatidyl-choline (POPC) lipid bilayer were studied. Two amphipathic α-helices with the sequence Ac-(LSLLLSL)<sub>3</sub>-NH<sub>2</sub> (LS2), and Ac-(LSSLLSL)<sub>3</sub>-NH<sub>2</sub> (LS3), which are known to form ion channels, were used. To investigate the surrounding lipid environment, we examined the hydrophobic mismatch, acyl chain order parameter profiles, lipid head-to-tail vector projection on the membrane surface, and the lipid headgroup vector projection. We find that the lipid structure is perturbed within approximately two lipid solvation shells from the protein bundle for each system (~15.0 Å). Beyond two lipid “solvation” shells bulk lipid bilayer properties were observed in all systems. To understand water flow, we enumerated each time a water molecule enters or exited the channel, which allowed us to calculate the number of water crossing events and their rates, and the residence time of water in the channel. We correlate the rate of water crossing with the structural properties of these ion channels and find that the movements of water are predominantly governed by the packing and pore diameter, rather than the topology of each peptide or the pore (hydrophobic or hydrophilic). We show that the crossing events of water fit quantitatively to a stochastic process and that water molecules are traveling diffusively through the pores. These lipid and water findings can be used for understanding the environment within and around ion channels. Furthermore, these findings can benefit various research areas such as rational design of novel therapeutics, in which the drug interacts with membranes and transmembrane proteins to enhance the efficacy or reduce off-target effects. |
| first_indexed | 2024-12-11T19:47:06Z |
| format | Article |
| id | doaj.art-24d8f47fb183429586f352ae91723cfa |
| institution | Directory Open Access Journal |
| issn | 2377-9098 |
| language | English |
| last_indexed | 2024-12-11T19:47:06Z |
| publishDate | 2018-03-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | AIMS Biophysics |
| spelling | doaj.art-24d8f47fb183429586f352ae91723cfa2022-12-22T00:52:52ZengAIMS PressAIMS Biophysics2377-90982018-03-0151507610.3934/biophy.2018.1.50biophys-05-01-050Molecular dynamics study of homo-oligomeric ion channels: Structures of the surrounding lipids and dynamics of water movementThuy Hien Nguyen0Catherine C. Moore1Preston B. Moore2Zhiwei Liu3Department of Chemistry & Biochemistry and the West Center for Computational Chemistry and Drug Design, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104, USADepartment of Chemistry & Biochemistry and the West Center for Computational Chemistry and Drug Design, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104, USADepartment of Chemistry & Biochemistry and the West Center for Computational Chemistry and Drug Design, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104, USADepartment of Chemistry & Biochemistry and the West Center for Computational Chemistry and Drug Design, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104, USAMolecular dynamics simulations were used to study the structural perturbations of lipids surrounding transmembrane ion channel forming helices/helical bundles and the movement of water within the pores of the ion-channels/bundles. Specifically, helical monomers to hexameric helical bundles embedded in palmitoyl-oleoyl-phosphatidyl-choline (POPC) lipid bilayer were studied. Two amphipathic α-helices with the sequence Ac-(LSLLLSL)<sub>3</sub>-NH<sub>2</sub> (LS2), and Ac-(LSSLLSL)<sub>3</sub>-NH<sub>2</sub> (LS3), which are known to form ion channels, were used. To investigate the surrounding lipid environment, we examined the hydrophobic mismatch, acyl chain order parameter profiles, lipid head-to-tail vector projection on the membrane surface, and the lipid headgroup vector projection. We find that the lipid structure is perturbed within approximately two lipid solvation shells from the protein bundle for each system (~15.0 Å). Beyond two lipid “solvation” shells bulk lipid bilayer properties were observed in all systems. To understand water flow, we enumerated each time a water molecule enters or exited the channel, which allowed us to calculate the number of water crossing events and their rates, and the residence time of water in the channel. We correlate the rate of water crossing with the structural properties of these ion channels and find that the movements of water are predominantly governed by the packing and pore diameter, rather than the topology of each peptide or the pore (hydrophobic or hydrophilic). We show that the crossing events of water fit quantitatively to a stochastic process and that water molecules are traveling diffusively through the pores. These lipid and water findings can be used for understanding the environment within and around ion channels. Furthermore, these findings can benefit various research areas such as rational design of novel therapeutics, in which the drug interacts with membranes and transmembrane proteins to enhance the efficacy or reduce off-target effects.http://www.aimspress.com/biophysics/article/1868/fulltext.htmlion channelswater fluxlipid perturbationsmembraneshelical bundles |
| spellingShingle | Thuy Hien Nguyen Catherine C. Moore Preston B. Moore Zhiwei Liu Molecular dynamics study of homo-oligomeric ion channels: Structures of the surrounding lipids and dynamics of water movement AIMS Biophysics ion channels water flux lipid perturbations membranes helical bundles |
| title | Molecular dynamics study of homo-oligomeric ion channels: Structures of the surrounding lipids and dynamics of water movement |
| title_full | Molecular dynamics study of homo-oligomeric ion channels: Structures of the surrounding lipids and dynamics of water movement |
| title_fullStr | Molecular dynamics study of homo-oligomeric ion channels: Structures of the surrounding lipids and dynamics of water movement |
| title_full_unstemmed | Molecular dynamics study of homo-oligomeric ion channels: Structures of the surrounding lipids and dynamics of water movement |
| title_short | Molecular dynamics study of homo-oligomeric ion channels: Structures of the surrounding lipids and dynamics of water movement |
| title_sort | molecular dynamics study of homo oligomeric ion channels structures of the surrounding lipids and dynamics of water movement |
| topic | ion channels water flux lipid perturbations membranes helical bundles |
| url | http://www.aimspress.com/biophysics/article/1868/fulltext.html |
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