Anomalous Diffraction Analysis of Biomolecular Structure

生物分子结构的反常衍射分析

基本信息

批准号：
8697562
负责人：
WAYNE A. HENDRICKSON
金额：
$ 46.37万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-03 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8697562
关键词：
Address Automation Basic Science Biological Calcium Caring Cluster Analysis Communities Complex Computer software DNA Data Data Collection Data Set Development Drug Formulations Electrons Evaluation Health Heart failure Human Indium Infection Lasers Light Malignant Neoplasms Measures Medical Membrane Proteins Methods Modeling Molecular Chaperones Neurodegenerative Disorders New York Noise Phase Philosophy Phosphorus Probability Procedures Process Proteins Radiation Refractory Research Resolution Signal Transduction Solutions Solvents Source Structure Sulfur Synchrotrons System Testing absorption base beamline biological systems computerized tools design detector experience improved instrumentation macromolecule meetings method development microbial novel strategies programs protein-histidine kinase public health relevance radiation effect receptor research study structural biology structural genomics technology development three dimensional structure tool

Address Automation Basic Science Biological Calcium Caring Cluster Analysis Communities Complex Computer software DNA Data Data Collection Data Set Development Drug Formulations Electrons Evaluation Health Heart failure Human Indium Infection Lasers Light Malignant Neoplasms Measures Medical Membrane Proteins Methods Modeling Molecular Chaperones Neurodegenerative Disorders New York Noise Phase Philosophy Phosphorus Probability Procedures Process Proteins Radiation Refractory Research Resolution Signal Transduction Solutions Solvents Source Structure Sulfur Synchrotrons System Testing absorption base beamline biological systems computerized tools design detector experience improved instrumentation macromolecule meetings method development microbial novel strategies programs protein-histidine kinase public health relevance radiation effect receptor research study structural biology structural genomics technology development three dimensional structure tool

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项目摘要

DESCRIPTION (provided by applicant): The overall objective of the proposed research is to develop enhanced anomalous diffraction methods for analyzing structures of biological macromolecules. We build on our recent accomplishments at New York Structural Biology Center (NYSBC) beamlines at Brookhaven's National Synchrotron Light Source (NSLS) and worldwide experience showing that multiwavelength anomalous diffraction (MAD) and SAD, MAD's single-wavelength counterpart, now predominate for de novo determinations of three- dimensional structures for biological macromolecules. We propose to optimize SAD and MAD phasing procedures by meeting the demands of compelling applications to current problems of biological significance. Biologically exciting problems motivate the development of appropriate tools, and forefront methods accelerate the solution of structures for systems of biological and medical significance. The overall objective is embodied in four specific aims: (1) we propose to enhance SAD phasing procedures for challenging problems such as selenomethionyl proteins at low resolution and only-light-atom native structures. A focus is on improved methods for increasing signal-to-noise ratios for anomalous diffraction by combining data from many crystals. (2) We propose to enhance MAD procedures for accurate experimental phase evaluation. Data collection strategies will be devised to mitigate radiation damage and minimize systematic errors. (3) We propose to develop procedures for low-energy anomalous diffraction experiments. We will develop experimental procedures and design instrumentation for low-energy (3 - 7 keV) experiments aiming to enhance anomalous signal from light atoms such as sulfur and phosphorous. (4) We propose to develop automation and enhanced procedures to facilitate SAD and MAD analyses from many crystals. A first priority is to encode and disseminate our current multi-crystal SAD process in convenient software.

描述（由申请人提供）：拟议研究的总体目标是开发增强的异常衍射方法，用于分析生物大分子的结构。 We build on our recent accomplishments at New York Structural Biology Center (NYSBC) beamlines at Brookhaven's National Synchrotron Light Source (NSLS) and worldwide experience showing that multiwavelength anomalous diffraction (MAD) and SAD, MAD's single-wavelength counterpart, now predominate for de novo determinations of three- dimensional structures for biological macromolecules.我们建议通过满足对当前生物学意义问题的强制性应用的要求来优化悲伤和疯狂的分阶段程序。生物学上令人兴奋的问题激发了适当的工具的开发，而前沿方法可以加快生物学和医学意义系统的结构解决方案。总体目标体现在四个具体目的中：（1）我们建议增强诸如低分辨率和唯一光明原子天然结构的挑战性问题（例如硒甲甲基蛋白）的挑战性问题。通过组合来自许多晶体的数据，重点是改进的方法，用于提高信噪比的异常衍射。（2）我们建议增强MAD程序以进行准确的实验阶段评估。数据收集策略将设计以减轻辐射损害并最大程度地减少系统错误。（3）我们建议开发用于低能量异常衍射实验的程序。我们将开发实验程序和设计仪器，用于低能（3-7 KEV）实验，旨在增强硫和磷等光原子的异常信号。（4）我们建议开发自动化和增强程序，以促进许多晶体的悲伤和疯狂分析。首要任务是在方便软件中编码和传播我们当前的多晶体SAD过程。