RAPID: IIBR Informatics: Predicting All-atom Structure of SARS-CoV-2 Related Protein Complex from 3D Cryo-Electron Microscopy Data

新型冠状病毒病(新冠肺炎)的暴发已造成全球大流行。了解新型冠状病毒(SARS-CoV-2)相关蛋白质复合体的分子基础对于深入了解该病毒及其如何感染人类细胞至关重要，这是开发抗击SARS-CoV-2的新药和疫苗的第一步。这项研究将使开发冠状病毒相关蛋白质复合体的全原子结构预测成为可能，包括病毒感染的人类细胞的复杂表面。预测结果将通过交互式网络应用程序广泛和迅速地传播，以最大限度地发挥研究的影响。这些成果将导致广泛的生物医学应用，例如更好地了解重要的生物功能、疾病过程、开发新的药物和疫苗，以及改进预防疗法，从而降低医疗保健成本。该项目旨在研究基于电子冷冻显微镜(Cryo-EM)的冠状病毒相关蛋白质复合体的从头算全原子结构预测。方法基于最先进的图像处理技术对数据进行预处理，深度学习用于复杂结构预测，动态优化用于最终精细化，以揭示冠状病毒相关大分子的基本机制。该项目还将提供一个开放源码的互动网络门户，供公众使用所开发的工具。这项工作可能会对为阻止SARS-CoV-2传播和目前的大流行而采取的步骤产生立竿见影的影响。还将为各级学生，特别是妇女和代表性不足的少数群体提供培训机会。该项目的结果可以在：http://faculty.washington.edu/dongsi.This快速奖是由生物基础设施部的基础设施创新生物研究(IIBR信息学)计划，使用冠状病毒援助，救济和经济安全(CARE)法案的资金。该奖项反映了美国国家科学基金会的法定使命，并已被认为值得支持，通过使用基金会的智力价值和更广泛的影响审查标准进行评估。

The outbreak of novel coronavirus disease (COVID-19) has caused a global pandemic. Knowledge on the molecular basis of novel coronavirus (SARS-CoV-2) related protein complexes is essential to providing insight of the virus and how it infects human cells, a first step in developing novel drugs and vaccines to combat SARS-CoV-2. This study will enable development of all-atom structure prediction of CoV-related protein complexes, including complex surfaces of human cells the virus infects. Prediction results will be broadly and quickly disseminated through interactive web applications to maximize the impact of the research. The results will lead to a broad range of biomedical applications, such as a better understanding of important biological functions, disease processes, development of novel drugs and vaccines, and improved preventive therapies leading to reduced health care costs. The project seeks to study ab initio all-atom structure prediction of CoV-related protein complexes based on electron cryo-microscopy (cryo-EM). Methods based on the state-of-the-art technologies of image processing for pre-processing the data, deep learning for complex structure prediction, and dynamic optimization for final refinement to reveal fundamental mechanisms of CoV-related macromolecules will be developed. The project will also provide an open-source and interactive web portal for public access of the developed tools. The work could have immediate impact on steps taken to halt the spread of SARS-CoV-2 and the current pandemic. Training opportunities for students at all levels, particularly women and underrepresented minorities will also be carried out. The results of the project can be found at: http://faculty.washington.edu/dongsi.This RAPID award is made by the Infrastructure Innovation for Biological Research (IIBR Informatics) Program in the Division of Biological Infrastructure, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.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.