CIBR: Integrative Computational Platform for Biomolecular Solid-State NMR

X射线晶体学、低温电子显微镜和核磁共振光谱是以原子或近原子分辨率确定蛋白质结构的主要方法。NMR光谱学是独特的，它能够支持在各种生理相关条件下在原子水平上研究蛋白质结构和动力学。溶液NMR适用于研究小到中等大小的蛋白质，并且不需要蛋白质结晶。然而，溶液NMR不适合于较大和较难溶解的蛋白质，如纳米/微晶球状蛋白质，膜蛋白质和原纤维的研究。这些系统非常有趣，因为它们与许多无法治愈的疾病有关。此类系统越来越适合固态核磁共振（ssNMR）。该项目旨在建立网络基础设施，通过开发和传播直观的软件包，自动分析算法，为结构计算提供计算资源的网络服务和教育视频，快速可靠地分析ssNMR数据。网络基础设施将提高固态NMR研究的效率和再现性，简化数据库中的存档或结果，并协助培训该领域的新人。固态NMR研讨会也计划开发，这为学生，博士后和初级教师提供实践培训后，这个项目相当于我们已经进行了十多年的解决方案NMR完成。结构生物学极大地受益于固态NMR仪器的最新进展，如超高速MAS（魔角旋转）和实验技术，包括N维实验中的质子或碳-13检测沿着稀疏采样和光谱重建。固态NMR收集的数据集，导致共振分配和结构测定是完全不同的，从溶液NMR中使用的。该项目的目标是开发一个强大而高效的端到端计算平台; a.为基于ssNMR的蛋白质研究开发自动化平台。B.开发用于生物分子ssNMR数据分析的图形用户界面（GUI）。C.为生物分子ssNMR提供网络服务和公共资源。该软件和相关教育材料将通过NMRFAM网络服务（www.example.com）、NMRbox项目（www.example.com）和SBGrid联盟（www.example.com）免费传播。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

X-ray crystallography, cryo-electron microscopy, and NMR spectroscopy are the leading methods for determining protein structures at atomic or near-atomic resolution. NMR spectroscopy is unique in its ability to support studies of protein structure and dynamics at the atomic level under a variety of physiologically relevant conditions. Solution NMR is suitable for investigations of small to moderate size proteins and does not require protein crystallization. However, solution NMR is unsuitable for studies of larger and less soluble proteins, such as nano/microcrystalline globular proteins, membrane proteins, and fibrils. These systems are of great interest because they are related to many diseases with no cure. Such systems are becoming increasingly amenable to solid-state NMR (ssNMR). This project aims to establish cyberinfrastructure for fast and reliable analysis of ssNMR data through the development and dissemination of intuitive software packages, algorithms for automated analysis, web services providing computational resources for structure calculations, and educational videos. The cyberinfrastructure will increase the efficiency and reproducibility of solid-state NMR studies, simplify the archiving or results in databases, and assist in the training of newcomers to the field. Solid-state NMR workshops are also planned to be developed, which provide hands-on training for student, postdocs, and junior faculties after completion of this project equivalent to the ones that we have carried longer than a decade for solution NMR. Structural biology is benefiting greatly from recent advances in solid-state NMR instrumentation, such as ultra-high-speed MAS (magic angle spinning), and experimental technology, including proton or carbon-13 detection in N-dimensional experiments along with sparse sampling and spectral reconstruction. The data sets collected for solid-state NMR that lead to resonance assignments and structure determinations are quite different from those used in solution NMR. The objectives of this project are to develop a robust and efficient, end-to-end computational platform; a. To develop an automation platform for ssNMR-based protein research. b. To develop graphical user interfaces (GUIs) for the analysis of biomolecular ssNMR data. c. To produce web services and public resources for biomolecular ssNMR. The software and related educational materials will be freely disseminated by NMRFAM web services (www.nmrfam.wisc.edu), the NMRbox Project (www.nmrbox.org), and the SBGrid Consortium (www.sbgrid.org).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.