MADMAX: PRECISE MEASUREMENT OF CONFORMATIONAL CHANGES IN PROTEINS

MADMAX：精确测量蛋白质构象变化

• 批准号: 7954934
• 负责人: LEE MAKOWSKI
• 金额: $ 2.61万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954934
• 关键词: Biological Process; Biophysics; Chemicals; Computer Retrieval of Information on Scientific Projects Database; Detection; Development; Disease; Funding; Goals; Grant; Institution; Label; Length; Ligand Binding; Ligands; Measurement; Measures; Mechanics; Membrane Proteins; Methods; Molecular; Movement; Positioning Attribute; Protein Dynamics; Proteins; Research; Research Personnel; Resolution; Resources; Roentgen Rays; Solutions; Source; Techniques; Time; United States National Institutes of Health; aqueous; macromolecule; millisecond; protein folding; protein function; vector

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project involves development of a new method, Multi-wavelength Anomalous Diffraction using Medium Angle X-ray solution scattering (MADMAX), for the precise measurement of interatomic distances within proteins and other macromolecules in aqueous solution. It will make possible the characterization of structural changes and intra-molecular movements that cannot be studied by existing techniques. Proteins are dynamic molecules whose activities contribute to all biological processes. Virtually all protein function requires intra-molecular movement, whether for the application of mechanical force, chemical transformation or molecular translocation. MADMAX will make possible accurate atomic-level measurement of these movements within proteins in solution. MADMAX should be generally applicable to macromolecules in solution and capable of elucidating protein action during a broad range of phenomena including allosteric interactions; protein-ligand interactions; channel gating; domain movements; and protein folding. It should be capable of measuring changes in the length of interatomic vectors with an accuracy of up to ~1 ¿. It can be adapted for time-resolved studies  to at least millisecond resolution. The goals of this project are: (i) Demonstrate the accurate measurement of anomalous differences in solution scattering from well characterized proteins. (ii) Predict the anomalous differences from atomic coordinate sets. (iii) Determine the limitations of the method: How large a protein is this method applicable to? How many labels are required for detection? How much disorder in the label position can be tolerated? (iv) Use MADMAX for precise measurement of structural changes due to ligand binding. (v) Use MADMAX for the study of structural changes in membrane proteins. This project involves development of a new method, Multi-wavelength Anomalous Diffraction using Medium Angle X-ray solution scattering (MADMAX), for the precise measurement of interatomic distances within proteins and other macromolecules in aqueous solution. It will make possible the characterization of structural changes and intra-molecular movements that cannot be studied by existing techniques. Proteins are dynamic molecules whose activities contribute to all biological processes. Virtually all protein function requires intra-molecular movement, whether for the application of mechanical force, chemical transformation or molecular translocation. MADMAX will make possible accurate atomic-level measurement of these movements within proteins in solution. MADMAX should be generally applicable to macromolecules in solution and capable of elucidating protein action during a broad range of phenomena including allosteric interactions; protein-ligand interactions; channel gating; domain movements; and protein folding. It should be capable of measuring changes in the length of interatomic vectors with an accuracy of up to ~1 ¿. It can be adapted for time-resolved studies  to at least millisecond resolution. The goals of this project are: (i) Demonstrate the accurate measurement of anomalous differences in solution scattering from well characterized proteins. (ii) Predict the anomalous differences from atomic coordinate sets. (iii) Determine the limitations of the method: How large a protein is this method applicable to? How many labels are required for detection? How much disorder in the label position can be tolerated? (iv) Use MADMAX for precise measurement of structural changes due to ligand binding. (v) Use MADMAX for the study of structural changes in membrane proteins.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 该项目涉及使用中角X射线溶液散射（MADMAX）的新方法的多波长异常衍射的开发，以精确测量水溶液中蛋白质和其他大分子内的原子间距离。这将使无法通过现有技术研究结构变化和分子内运动的表征。蛋白质是动态分子，其活性有助于所有生物学过程。几乎所有蛋白质功能都需要分子内运动，无论是用于应用机械力，化学转化还是分子翻译。 Madmax将使蛋白质中这些运动中这些运动的准确原子水平测量可能。 Madmax通常应适用于溶液中的大分子，并且能够在包括变构相互作用的广泛现象中阐明蛋白质作用；蛋白质 - 配体相互作用；通道门控；域运动；和蛋白质折叠。它应该能够测量原子间载体长度的变化，其精度高达〜1。它可以适应时间分辨的研究至少毫秒分辨率。 该项目的目标是： （i）证明了从良好表征蛋白质中溶液散射的异常差异的准确测量。 （ii）预测原子坐标集的异常差异。 （iii）确定方法的局限性：该方法适用于多大的蛋白质？检测需要多少个标签？可以容忍标签位置有多少疾病？ （iv）使用Madmax精确测量由于配体结合而引起的结构变化。 （v）使用MADMAX研究膜蛋白的结构变化。 该项目涉及使用中角X射线溶液散射（MADMAX）的新方法的多波长异常衍射的开发，以精确测量水溶液中蛋白质和其他大分子内的原子间距离。这将使无法通过现有技术研究结构变化和分子内运动的表征。蛋白质是动态分子，其活性有助于所有生物学过程。几乎所有蛋白质功能都需要分子内运动，无论是用于应用机械力，化学转化还是分子翻译。 Madmax将使蛋白质中这些运动中这些运动的准确原子水平测量可能。 Madmax通常应适用于溶液中的大分子，并且能够在包括变构相互作用的广泛现象中阐明蛋白质作用；蛋白质 - 配体相互作用；通道门控；域运动；和蛋白质折叠。它应该能够测量原子间载体长度的变化，其精度高达〜1。它可以适应时间分辨的研究至少毫秒分辨率。 该项目的目标是： （i）证明了从良好表征蛋白质中溶液散射的异常差异的准确测量。 （ii）预测原子坐标集的异常差异。 （iii）确定方法的局限性：该方法适用于多大的蛋白质？检测需要多少个标签？可以容忍标签位置有多少疾病？ （iv）使用Madmax精确测量由于配体结合而引起的结构变化。 （v）使用MADMAX研究膜蛋白的结构变化。