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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目涉及开发一种新方法，即使用中角X射线溶液散射的多波长异常衍射（MADMAX），用于精确测量水溶液中蛋白质和其他大分子的原子间距离。 它将使现有技术无法研究的结构变化和分子内运动的表征成为可能。 蛋白质是动态分子，其活动有助于所有生物过程。几乎所有的蛋白质功能都需要分子内运动，无论是机械力的应用，化学转化还是分子移位。 MADMAX将使在溶液中蛋白质内这些运动的精确原子水平测量成为可能。 MADMAX应普遍适用于溶液中的大分子，并能够阐明蛋白质在广泛现象期间的作用，包括变构相互作用;蛋白质-配体相互作用;通道门控;结构域运动;和蛋白质折叠。 它应该能够测量原子间矢量长度的变化，精度高达~1 ½。 它可以适用于时间分辨的研究  到毫秒级的分辨率。 该项目的目标是： (i)演示如何准确测量表征蛋白质的溶液散射中的异常差异。 (ii)从原子坐标系预测异常差异。 (iii)确定该方法的局限性：该方法适用于多大的蛋白质？ 检测需要多少个标签？ 标签位置的混乱程度是可以容忍的？ (iv)使用MADMAX精确测量配体结合引起的结构变化。 (v)使用MADMAX研究膜蛋白的结构变化。 该项目涉及开发一种新方法，即使用中角X射线溶液散射的多波长异常衍射（MADMAX），用于精确测量水溶液中蛋白质和其他大分子的原子间距离。 它将使现有技术无法研究的结构变化和分子内运动的表征成为可能。 蛋白质是动态分子，其活动有助于所有生物过程。几乎所有的蛋白质功能都需要分子内运动，无论是机械力的应用，化学转化还是分子移位。 MADMAX将使在溶液中蛋白质内这些运动的精确原子水平测量成为可能。 MADMAX应普遍适用于溶液中的大分子，并能够阐明蛋白质在广泛现象期间的作用，包括变构相互作用;蛋白质-配体相互作用;通道门控;结构域运动;和蛋白质折叠。 它应该能够测量原子间矢量长度的变化，精度高达~1 ½。 它可以适用于时间分辨的研究  到毫秒级的分辨率。 该项目的目标是： (i)演示如何准确测量表征蛋白质的溶液散射中的异常差异。 (ii)从原子坐标系预测异常差异。 (iii)确定该方法的局限性：该方法适用于多大的蛋白质？ 检测需要多少个标签？ 标签位置的混乱程度是可以容忍的？ (iv)使用MADMAX精确测量配体结合引起的结构变化。 (v)使用MADMAX研究膜蛋白的结构变化。