Computational Tools for Neutron Protein Crystallography

描述（由申请人提供）： 本计画的目标是发展一套中子蛋白质结晶学的计算工具。在资助期开始时，我们将专注于提供可以立即应用于解决中子蛋白质晶体学计算瓶颈的工具，并确定一系列蛋白质的中子结构，其中许多蛋白质具有很高的生物医学重要性，跨越了一系列的大小和复杂性。最终的目标是将这些计算工具作为可扩展的C++模块和数据库整合到PHENIX（基于Python的集成Xtallography分层环境）中，用于自动化大分子晶体学。该软件将使用并促进计算晶体学实验室（cctbx）中X射线晶体学的基本编程工具。我们的愿景是为具有一系列晶体学经验的结构生物学家提供一个计算工作台，可以用于中子或X射线蛋白质晶体学。计算工具将把中子强度数据定标、合并、波长归一化、衰减校正和处理、相位计算、地图生成和解释、模型建立和改进所需的所有任务整合到一个系统中。自动决策概念将最大限度地减少人为干预，并减少优化结构所需的时间。软件将推广到X射线蛋白质晶体学。结构细化工具将允许针对中子、X射线和能量最小化函数的任何组合对蛋白质结构进行全局细化。结构生物学家将以可互操作的方式使用同一系统进行X射线、中子或X射线和中子联合分析。

DESCRIPTION (provided by applicant): The aim of this project is to develop a set of computational tools for neutron protein crystallography. At the start of the funding period we will focus on providing tools that can be immediately applied to address the computational bottleneck in neutron protein crystallography and to determine the neutron structures of a series of proteins, many with high biomedical importance that span a spectrum of size and complexity. The ultimate aim is to adapt these computational tools for incorporation into PHENIX (Python-based Hierarchical EnviroNment for Integrated Xtallography) for automated macromolecular crystallography as extensible C++ modules and databases. The software will use and contribute towards basic programming tools for X-ray crystallography in the Computational Crystallography Toolbox (cctbx). Our vision is to contribute to a computational workbench that structural biologists, with a range of crystallographic experience, can use alternatively for neutron or X-ray protein crystallography. The computational tools will integrate all tasks required for neutron intensity data scaling, merging, wavelength normalization, attenuation correction and handling, computation of phases, map generation and interpretation, model building and refinement into one system. Automatic decision making concepts will minimize human interventions and decrease the time needed to refine structures. Software will be generalizable to X-ray protein crystallography. The structure refinement tools will allow global refinement of protein structures against any combination of neutron, X-ray and energy minimization functions. Structural biologists will use the same system in an interoperable way for X-ray, neutron or joined X-ray and neutron analyses.