Self Assembled Lipid Icosohedra for Highthroughput Membrane Protein Structure Det

用于高通量膜蛋白结构检测的自组装脂质二十面体

• 批准号: 7659632
• 负责人: Michael H. B. Stowell
• 金额: $ 30.3万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7659632
• 关键词: Categories; Disease; Drug Design; Electron Microscopy; Future; Human; Laboratories; Lipids; Membrane Proteins; Methods; Pharmacologic Substance; Proteins; Structure; Validation; base; novel; novel strategies; particle; protein structure; success

DESCRIPTION (provided by applicant): This proposal aims to minimize the three bottlenecks of membrane proteins structure determination with a novel approach that combines high throughput electron microscopy single particle analysis with a novel self-assembling method. Validation of this approach will be realized by application to the structural analysis of several proteins which represent major categories of eukaryotic membrane proteins of biomedical importance. The overall objective of this proposal will be determining their structures and to simultaneously fully develop this approach to tackle further membrane protein targets in our own and other laboratories. The majority of known human pharmaceutical targets are membrane proteins and the future success of structure based drug design efforts will rely heavily on membrane protein structural information. This proposal will minimize the three bottlenecks of membrane proteins structure determination with a novel approach that combines high throughput electron microscopy single particle analysis with a novel self-assembling method. The success of this project will lower the barrier for obtaining the needed information for structure based drug design to proceed for a wide range of diseases.

描述（由申请人提供）：该提案旨在通过将高通量电子显微镜单颗粒分析与新型自组装方法相结合的新方法，最大限度地减少膜蛋白结构测定的三个瓶颈。这种方法的验证将通过应用于几种蛋白质的结构分析来实现，这些蛋白质代表了具有生物医学重要性的真核生物膜蛋白的主要类别。该提案的总体目标将是确定它们的结构，同时充分开发这种方法，以在我们自己的实验室和其他实验室中解决更多的膜蛋白靶点。大多数已知的人类药物靶标是膜蛋白，并且基于结构的药物设计工作的未来成功将严重依赖于膜蛋白结构信息。这一建议将最大限度地减少膜蛋白结构测定的三个瓶颈与一种新的方法，结合高通量电子显微镜单粒子分析与一种新的自组装方法。该项目的成功将降低获得基于结构的药物设计所需信息的障碍，以针对广泛的疾病进行设计。