MAD USING MEDIUM ANGLE X-RAY SOLUTION SCATTERING (MADMAX)

使用中角 X 射线溶液散射 (MADMAX) 进行 MAD

• 批准号: 8168634
• 负责人: LEE MAKOWSKI
• 金额: $ 2.15万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168634
• 关键词: Award; Computer Retrieval of Information on Scientific Projects Database; Funding; Grant; Hemoglobin; Institution; Iron; Label; Measurement; Measures; Methods; Modeling; Pattern; Potassium Channel; Proteins; Research; Research Personnel; Resources; Roentgen Rays; Selenium; Selenomethionine; Solutions; Source; Structure; Testing; United States National Institutes of Health; Water; Work; aqueous; innovation; macromolecule; protein structure; research study; technique development

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 use of a new method, Multi-wavelength Anomalous Diffraction (MADMAX) using Medium Angle X-ray solution scattering (MADMAX), for the precise measurement of interatomic distances within proteins and other macromolecules in aqueous solution. Our preliminary experiments have shown that anomalous differences can be measured from proteins in solution. Differences from selenium scatter have been observed in solution scattering from the potassium channel, kcsa; differences from iron have been observed in scattering from hemoglobin. The work is supported by an NIH Eureka award (for highly innovative research) to support the development of this technique. Recently, we developed a method for computing wide-angle x-ray solution scattering (WAXS) from atomic coordinate sets using an explicit atom representation of water (Park et al.,2009). This, which requires no fitting of parameters) allows us to calculate WAXS patterns to within experimental error to test models for protein structure. We have now extended that capability to include calculation of the anomalous scattering components of proteins (Bardhan and Makowski, unpublished). This greatly increases the power of MADMAX, allowing us to predict the anomalous differences when there are multiple anomalous scattering atoms in the protein. Currently we are collecting anomalous scattering from selenomethionine-labelled proteins of known structure to determine the power of the method for proteins with 1 or 2 or 6-10 selenium labels.

该副本是利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，这不一定是调查员的机构。 该项目涉及使用一种新方法，即使用中角X射线溶液散射（MADMAX）的多波长异常衍射（MADMAX），以精确测量水溶液中蛋白质和其他大分子内原子间距离。我们的初步实验表明，可以从溶液中的蛋白质中测量异常差异。在从钾通道KCSA的溶液散射中观察到了与硒散射的差异。在血红蛋白的散射中已经观察到了铁的差异。这项工作得到了NIH Eureka奖（高度创新研究）的支持，以支持该技术的开发。最近，我们开发了一种使用水的显式原子代表来计算原子坐标集的广角X射线溶液散射（蜡）的方法（Park等，2009）。 这不需要参数的拟合）使我们能够在实验误差内计算蜡模式，以测试蛋白质结构的模型。 现在，我们已经扩展了该功能包括计算蛋白质（Bardhan和Makowski，未发表）的异常散射成分。 这大大增加了Madmax的力量，从而使我们可以预测蛋白质中有多个异常散射原子时的异常差异。 目前，我们正在从已知结构的硒甲米汀标记的蛋白质中收集异常散射，以确定具有1或2或6-10硒标签的蛋白质方法的功率。