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

人类 Nav1.1 钠通道：具有疾病相关突变的同源物的结构、功能、药物结合和分子动力学

• 批准号: 2087560
• 金额: --
• 依托单位: Birkbeck, University of London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2087560
• 关键词: human; Nav1.1; sodium; channel; Structure

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.

电压门控钠通道（Navs）在神经信号传递中起着至关重要的作用，因为它们的打开启动了动作电位。人类hNav1.1异构体的突变会产生一系列疾病，包括癫痫。因此，hNav1.1代表了药物开发的关键目标。使用与hNav1.1具有高度相似的结构和功能特性的原核navm（其晶体结构已经确定），学生将创建与hNav1.1疾病相关的突变体，并使用晶体学，低温电子显微镜，分子动力学计算以及生物物理，生化和功能表征在分子水平上检查其影响，利用这些信息探索潜在的新候选药物。