DIALS: New Computational Methods to Enable Challenging Crystallographic Experiments

DIALS：新的计算方法可实现具有挑战性的晶体学实验

基本信息

批准号：
9242823
负责人：
NICHOLAS K SAUTER
金额：
$ 3.15万
依托单位：
UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-01 至 2017-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9242823
关键词：
Algorithms Architecture Biochemical Biological Cells Communities Complement Computer software Computing Methodologies Consensus Consumption Coupled Crystallography Data Data Collection Data Set Detection Disease Generations Goals Grant Growth Health Human Image Individual Life Light Maps Measurement Measures Metals Methods Microscopic Modeling Molecular Conformation Molecular Structure Needles Nucleic Acids Pattern Phase Physiologic pulse Physiological Powder dose form Process Proteins Protocols documentation Publications Radiation Reaction Resolution Roentgen Rays Rotation Sampling Scientist Shapes Signal Transduction Source Specimen Spottings Structure Sulfur Synchrotrons Techniques Technology Temperature Testing Time United States National Institutes of Health Work X-Ray Crystallography amyloid peptide base beamline computerized data processing data reduction design detector electron density experimental analysis free-electron laser imaging detector improved instrumentation metalloenzyme open source physical model physical property programs protein structure public health relevance radiation effect research study submicron synchrotron radiation two-dimensional

项目摘要

DESCRIPTION (provided by applicant): Basic biochemical mechanisms fundamental to human health arise from understanding the structure of large biological molecules, both proteins and nucleic acids. X-ray crystallography has been a key method for uncovering their structure and function. This project will develop computational methods needed to enable the use of serial X-ray crystallography techniques. Serial crystallography, performed at either third generation synchrotron beamlines or X-ray free-electron lasers, is emerging as a way to determine molecular structure using crystals that are probed once with a short X-ray pulse and then exchanged for a new sample. This a departure from traditional single-crystal experiments where the crystal is rotated in the beam to assemble a full data set, but which require large crystals, coupled with cryocooling to slow down the effects of radiation damage. Serial crystallography, in contrast, is performed with an extremely short X-ray pulse, which probes the structure before radiation damage occurs, and at normal physiological temperatures, where the full range of available molecular conformations can be revealed. The program DIALS (Diffraction Integration for Advanced Light Sources) reduces crystal diffraction patterns to a list of Bragg spot intensities, which are needed to compute the electron density map leading to an atomic model. Because the diffraction pattern in serial crystallography is sampled from still crystals rather than rotating ones, the analysis of Bragg spot intensities is entirely different. Frst, a correction must be applied to convert the intensity to the equivalent observation from a single rotating crystal, then duplicate Bragg spot measurements from potentially thousands of crystals must be merged to derive a single complete data set. This project will explore the assumptions made during this data reduction process, and identify optimal physical models and algorithms for deriving the best merged data. At the same time, DIALS will be released as a general data reduction package for all synchrotron-based crystallography (for both serial and single-crystal methods). DIALS is built around an open- source, community-oriented software architecture that can be adapted by beamline scientists to accommodate new instrumentation, in a field where rapid hardware advances are expected to continue for many years.

描述（由申请人提供）：对人类健康至关重要的基本生化机制源于对蛋白质和核酸等大生物分子结构的了解，X射线晶体学是揭示其结构和功能的关键方法。使用串行 X 射线晶体学技术所需的计算方法，在第三代同步加速器光束线或 X 射线自由电子激光器上进行，正在成为一种使用晶体确定分子结构的方法。用短 X 射线脉冲探测一次，然后更换新样品，这与传统的单晶实验不同，在传统的单晶实验中，晶体在光束中旋转以组装完整的数据集，但需要大晶体耦合。相比之下，串行晶体学是用极短的 X 射线脉冲进行的，它可以在辐射损伤发生之前在正常的生理温度下探测结构，其中可用分子的全部范围。构象可以程序 DIALS（高级光源的衍射集成）将晶体衍射图案简化为一个列表。布拉格点强度，这是计算形成原子模型的电子密度图所需的。因为连续晶体学中的衍射图案是从静止晶体而不是旋转晶体中采样的，所以布拉格点强度的分析完全不同。必须应用校正将强度转换为单个旋转晶体的等效观测值，然后必须合并来自潜在数千个晶体的重复布拉格点测量以获得单个完整数据集。该项目将探索在此数据期间所做的假设。同时，DIALS 将作为所有基于同步加速器的晶体学（适用于串行和单晶方法）的通用数据缩减包发布。围绕开源、面向社区的软件架构构建，光束线科学家可以对其进行调整，以适应新的仪器，在硬件快速发展的领域预计将持续多年。