Computational Tools for Neutron Protein Crystallography

项目描述（由申请人提供）：本项目旨在继续发明、完善和应用中子蛋白晶体学的通用计算工具。我们的主要重点将是提供创新但实用的解决方案，这些解决方案可以快速部署到目标用户社区，以解决中子蛋白晶体学中的计算瓶颈，并确定一系列蛋白质的中子结构，其中许多具有高度生物医学重要性，跨越大小和复杂性的光谱。我们将继续我们目前的工作，将这些计算工具整合到PHENIX（基于Python的集成Xtallography分层环境）中，作为可扩展的c++和Python模块实现自动晶体学。该软件将使用并为计算晶体学工具箱（cctbx）中的晶体学基本编程工具做出贡献。我们的愿景是为具有晶体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，x射线或全局中子/ x射线/能量晶体学。计算工具将把处理中子强度数据缩放、波长归一化、衰减校正和处理、相位的确定和计算、地图生成和多地图表示的创新解决方案、自动地图解释、模型构建和细化所需的所有任务集成到一个系统中。自动决策概念将最大限度地减少人为干预，减少优化结构所需的时间。我们的软件开发也将推广到x射线晶体学。这些工具将允许结构确定、模型构建和针对中子、x射线和能量最小化功能的任何组合进行优化。结构生物学家将以一种可互操作的方式使用相同的系统，基于x射线、中子和能量数据进行结构确定和改进。

DESCRIPTION (provided by applicant): The aim of this project is to continue to invent, refine and apply generalizable computational tools for neutron protein crystallography. Our primary focus will be to provide innovative, but practical solutions, that can be rapidly deployed to the target user community 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. We will continue our current work adapting these computational tools for incorporation into PHENIX (Python-based Hierarchical Environment for Integrated Xtallography) for automated crystallography as extensible C++ and Python modules. The software will use and contribute towards the basic programming tools for crystallography in the Computational Crystallographic Toolbox (cctbx). Our vision is to contribute to a computational workbench that structural biologist, with a range of crystallographic experience, can use alternately for neutron, X-ray, or global neutron/X-ray/energy crystallography. The computational tools will integrate all tasks required for handling neutron intensity data scaling, wavelength normalization, attenuation correction and handling, determination and computation of phases, map generation and innovative solutions to multiple map representation, automated map interpretation, model building and refinement into one system. Automatic decision-making concepts will minimize human interventions and decrease time needed to refine structures. Our software developments will also be generalizable to X-ray crystallography. These tools will allow structure determination, model building, and refinement against any combination of neutron, X-ray and energy minimization functions. Structural biologists will use the same system in an interoperable way for structure determination and refinement based on X-ray, neutron and energetic data. PUBLIC HEALTH RELEVANCE: Neutron crystallography is a technique that provides unique types of information on the enzymatic function and drug binding properties of biological macromolecules that are highly relevant to public health. The aim of this project is to continue to invent, refine and apply generalizable computational tools that can be applied to address the computational bottlenecks in neutron protein crystallography and then to use those tools to study a series of proteins of high biomedical importance that span a spectrum of size and complexity.