The human Nav1.1 sodium channel: Structure, Function, Drug Binding and Molecular Dynamics of Homologues Bearing Disease-Related Mutations

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Title
The human Nav1.1 sodium channel: Structure, Function, Drug Binding and Molecular Dynamics of Homologues Bearing Disease-Related Mutations

CoPED ID
32998c4e-80be-49f6-8981-ab35922f720b

Status
Active

Funders

Value
No funds listed.

Start Date
Sept. 30, 2018

End Date
May 29, 2023

Description

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Voltage-gated sodium channels (Navs) play essential roles in nerve signal transmission, as their opening initiates the action potential. Mutations in the human hNav1.1 isoform produce a range of diseases, including epilepsy. hNav1.1 therefore represents a key target for pharmaceutical drug development. Using the prokaryotic NavMs (whose crystal structure we have determined), which has highly similar structural and functional properties to hNav1.1, the student will create mutants associated with hNav1.1 diseases, and examine their effects on a molecular level using crystallography, cryoEM, molecular dynamics calculations, and biophysical, biochemical, and functional characterizations, using this information to explore potential new drug candidates.

Birkbeck College LEAD_ORG

Bonnie Wallace SUPER_PER
Callum Haste STUDENT_PER

Subjects by relevance
  1. Medicinal substances

Extracted key phrases
  1. Human Nav1.1 sodium channel
  2. Human hnav1.1 isoform
  3. Hnav1.1 disease
  4. Homologues Bearing Disease
  5. Crystal structure
  6. Potential new drug candidate
  7. Drug Binding
  8. Nerve signal transmission
  9. Molecular dynamic calculation
  10. Molecular Dynamics
  11. Pharmaceutical drug development
  12. Action potential
  13. Related Mutations
  14. Functional property
  15. Functional characterization

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