CIBR: Integrative Computational Platform for Biomolecular Solid-State NMR

X射线结晶学、低温电子显微镜和核磁共振光谱学是在原子或近原子分辨率下确定蛋白质结构的主要方法。核磁共振光谱学的独特之处在于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的结构和动力学。溶液核磁共振适用于研究小到中等尺寸的蛋白质，不需要蛋白质结晶。然而，溶液核磁共振不适合研究较大和较难溶解的蛋白质，如纳米/微晶球状蛋白质、膜蛋白质和纤维。人们对这些系统非常感兴趣，因为它们与许多无法治愈的疾病有关。这类系统越来越容易受到固态核磁共振(ss核磁共振)的影响。该项目旨在通过开发和传播直观的软件包、自动分析的算法、为结构计算提供计算资源的网络服务和教育视频，为快速和可靠地分析核磁共振数据建立网络基础设施。网络基础设施将提高固态核磁共振研究的效率和可重复性，简化数据库中的存档或结果，并协助培训实地新人。还计划开发固态核磁共振研讨会，在该项目完成后为学生、博士后和初级教师提供实践培训，相当于我们开展的解决方案核磁共振超过十年的培训。结构生物学在很大程度上得益于固体核磁共振仪器的最新进展，如超高速MAS(魔角旋转)，以及实验技术，包括N维实验中的质子或碳13检测以及稀疏采样和光谱重建。为固体核磁共振收集的数据集导致共振指定和结构确定，与在溶液核磁共振中使用的数据集有很大不同。这个项目的目标是开发一个健壮高效的端到端计算平台；a.开发一个基于单核磁共振的蛋白质研究的自动化平台。B.开发用于分析生物分子单核磁共振数据的图形用户界面(GUI)。C.为生物分子单核磁共振提供网络服务和公共资源。该软件和相关教育材料将由NMRFAM网络服务(www.nmrlam.issc.edu)、NMRbox项目(www.nmrbox.org)和SBGrid联盟(www.sbgrid.org)免费分发。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.