权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

EAGER: Investigating the Hinge Mechanics of the Spike Protein to Understand the Coronavirus Infection Mechanism

EAGER：研究刺突蛋白的铰链机制以了解冠状病毒感染机制

基本信息

批准号：
2034584
负责人：
Sinan Keten
金额：
$ 18.8万
依托单位：
Northwestern University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-15 至 2021-11-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2034584&HistoricalAwards=false
关键词：
EAGER Investigating Hinge Mechanics Spike

项目摘要

This COVID-19 EArly-concept Grant for Exploratory Research (EAGER) project will investigate how SARS-CoV-2, virus causing the disease, attaches to cells, and how it may detach when subject to mechanical force. The virus attaches to cells through its spike protein, and it is believed that this protein has flexible regions called hinges that allow it to change its shape to regulate its attachment. This project will establish a method involving molecular simulations and data science methods to reliably identify these hinges. These analyses will aim to explain how mechanical forces and chemical factors influence hinge motions that influence the binding of the virus to cells. Understanding how the spike protein changes its shape during viral attachment, and how it may detach, e.g. during coughing and sneezing is critical for accurately describing how the virus enters cells, and how we can prevent infection. These findings will advance scientific understanding about this novel coronavirus and provide fundamental insights needed to find a cure for the disease. This research program will aim to implement a novel computational strategy to understand how hinge motions of the spike protein govern viral attachment. This method will combine molecular simulations with network reconstruction and community detection methods that are new to the study of proteins. It will aim to accurately identify soft and stiff regions of the protein, pinpoint hinge motions, and examine how mechanical forces impact receptor binding domain accessibility and binding strength. This will provide critically needed physical insights into how SARS-CoV-2 binds and infects cells, how it may dislodge when subject to force, and which compliant regions antibodies could target to prevent attachment. Statistically rigorous techniques for inferring network properties will help to correctly identify the regions that regulate viral attachment. As part of outreach efforts, physics-based animations and videos on the spike protein dynamics and viral attachment will be created and disseminated. Statistical methods, codes and software developed to infer networks and hinge motions from simulations will be shared with the research community.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.

这个COVID-19早期概念探索性研究资助（EAGER）项目将研究引起这种疾病的SARS-CoV-2病毒如何附着在细胞上，以及当受到机械力时如何分离。该病毒通过其刺突蛋白附着于细胞，据信这种蛋白质具有称为铰链的柔性区域，允许其改变形状以调节其附着。该项目将建立一种涉及分子模拟和数据科学方法的方法，以可靠地识别这些铰链。这些分析旨在解释机械力和化学因素如何影响铰链运动，从而影响病毒与细胞的结合。了解刺突蛋白在病毒附着期间如何改变其形状，以及它如何分离（例如在咳嗽和打喷嚏期间）对于准确描述病毒如何进入细胞以及我们如何预防感染至关重要。这些发现将促进对这种新型冠状病毒的科学理解，并为找到治愈这种疾病的方法提供所需的基本见解。这项研究计划旨在实施一种新的计算策略，以了解刺突蛋白的铰链运动如何控制病毒附着。这种方法将联合收割机分子模拟与网络重建和社区检测方法相结合，是新的蛋白质的研究。它的目标是准确地识别蛋白质的软和硬区域，精确定位铰链运动，并检查机械力如何影响受体结合结构域的可及性和结合强度。这将为SARS-CoV-2如何结合和感染细胞提供急需的物理见解，当受到力时它如何被驱逐，以及抗体可以靶向哪些顺应性区域以防止附着。严格的统计技术推断网络属性将有助于正确识别调节病毒附着的区域。作为外联工作的一部分，将制作和传播关于刺突蛋白动力学和病毒附着的基于物理学的动画和视频。该奖项反映了NSF的法定使命，并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，被认为值得支持。