Molecular dynamics simulations of the CLC-2 ion channel
Abstract/Contents
- Abstract
- This work reports a dynamical Markov state model of CLC-2 "fast" (pore) gating, based on 600 microseconds of molecular dynamics (MD) simulation. In the starting conformation of our CLC-2 model, both outer and inner channel gates are closed. The first conformational change in our dataset involves rotation of the inner-gate backbone along residues S168-G169-I170. This change is strikingly similar to that observed in the cryo-EM structure of the bovine CLC-K channel, though the volume of the intracellular (inner) region of the ion conduction pathway is further expanded in our model. From this state (inner gate open and outer gate closed), two additional states are observed, each involving a unique rotameric flip of the outer-gate residue GLUex. Both additional states involve conformational changes that orient GLUex away from the extracellular (outer) region of the ion conduction pathway. In the first additional state, the rotameric flip of GLUex results in an open, or near-open, channel pore. The equilibrium population of this state is low (about one percent), consistent with the low open probability of CLC-2 observed experimentally in the absence of a membrane potential stimulus (0 mV). In the second additional state, GLUex rotates to occlude the channel pore. This state, which has a low equilibrium population (about one percent), is only accessible when GLUex is protonated. Together, these pathways model the opening of both an inner and outer gate within the CLC-2 selectivity filter, as a function of GLUex protonation. Collectively, our findings are consistent with published experimental analyses of CLC-2 gating and provide a high-resolution structural model to guide future investigations.
Description
| Type of resource | software, multimedia |
|---|---|
| Date created | 2019 |
Creators/Contributors
| Author | McKiernan, Keri A. |
|---|---|
| Author | Koster, Anna K. |
| Author | Maduke, Merritt |
| Author | Pande, Vijay S. |
Subjects
| Subject | biophysics |
|---|---|
| Subject | Markov model |
| Subject | molecular dynamics |
| Subject | CLC-2 |
| Genre | Dataset |
Bibliographic information
| Related Publication | McKiernan, Keri A. and Koster, Anna K. and Maduke, Merritt and Pande, Vijay S. 2017. Dynamical model of the CLC-2 ion channel exhibits a two-step gating mechanism. bioRxiv https://www.biorxiv.org/content/10.1101/228163v4 |
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| Reassembly of Contents | Because of the size of this dataset, the .tar file has been broken into smaller pieces using the "split" command (https://en.wikipedia.org/wiki/Split_(Unix)). In order to use this data set, you will need to: |
| Reassembly of Contents | a) download each of the 14 constituent files on this page. For the large files, we suggest that you download them using 'wget' or 'curl'. A sample command to use for downloading one of the files: |
| Reassembly of Contents | `wget https://stacks.stanford.edu/file/druid:rq847qm8302/[insert filename]`. Files are quite large, so downloading will take a while, even if your connection is very fast. |
| Reassembly of Contents | b) run the command "cat [filename].tgz_* | tar xz" from the terminal |
| Reassembly of Contents | c) unarchive the tar file |
| Location | https://purl.stanford.edu/rq847qm8302 |
Access conditions
- Use and reproduction
- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).
Preferred citation
- Preferred Citation
- McKiernan, Keri A. and Koster, Anna K. and Maduke, Merritt and Pande, Vijay S. (2019). Molecular dynamics simulations of the CLC-2 ion channel. Stanford Digital Repository. Available at: https://purl.stanford.edu/rq847qm8302
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Folding@home Collection
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- Contact
- kmckiern@alumni.stanford.edu
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