Computational Tools for Neutron Protein Crystallography

描述(由申请人提供)： 该项目的目的是开发一套用于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的工具，以解决中子蛋白质结晶学中的计算瓶颈，并确定一系列蛋白质的中子结构，其中许多蛋白质具有高度的生物医学重要性，跨越了大小和复杂性的范围。最终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Xtallograph的分层环境)中，以实现自动化的大分子结晶学。该软件将使用并促进计算结晶学工具箱(Cctbx)中的X射线结晶学基本编程工具。我们的愿景是为拥有一系列结晶学经验的结构生物学家提供一个计算工作台，可以交替用于中子或X射线蛋白质结晶学。这些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，并减少改进结构所需的时间。软件将被推广到X射线蛋白质结晶学。结构优化工具将允许针对中子、X射线和能量最小化功能的任何组合对蛋白质结构进行全局优化。结构生物学家将以可互操作的方式使用相同的系统进行X射线、中子或联合X射线和中子分析。

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.