Collaborative Research: CIBR: Incorporating Crystallography and Cryo-EM Tools in Foldit

合作研究：CIBR：在 Foldit 中结合晶体学和冷冻电镜工具

• 批准号: 2051305
• 负责人: Scott Horowitz
• 金额: $ 31.34万
• 依托单位: University of Denver
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2051305&HistoricalAwards=false
• 关键词: Collaborative; Research; CIBR; Incorporating; Crystallography

The goal of structural biologists is to visualize biomolecules at atomic resolution, which is a critical step in understanding all aspects of biology, including diseases and their cures. The dominant experimental methods for structure determination, called Cryo-Electron Microscopy and X-Ray Crystallography, rely upon fitting the atoms from biological molecules into three-dimensional “maps”, seeking agreement with experimental data. This fitting process is laborious and difficult, but preliminary studies have shown that this task could be performed very effectively by citizen scientists playing the biochemistry computer game Foldit. As a premier citizen science computer game, Foldit has already been played by over 600,000 people since its inception. This project aims to improve the capabilities of Foldit to enable scientists and citizen scientists alike to accurately build biological structures of varying types and sizes. This capability could strongly improve science’s ability to understand the basis of many biological phenomena. In addition to these scientific benefits, this project benefits both science education and society as a whole. This new capability will enhance the variety and quality of educational options using Foldit, improving it as a major interface between the scientific community and society.There is an ongoing need for improvements for methods to solve crystal and cryo-EM structures. Foldit is a citizen science project in which users aid in many biochemistry problems, including model building and real space refinement in protein structure solving projects. Early tests suggest that these ventures produce high quality crystal and cryo-EM structures, but many improvements are needed to make Foldit a go-to option for structure solving problems. Recently, new versions of Foldit have been introduced that can be used by single scientists or lab groups, in addition to standard citizen science Foldit puzzles. These options will be leveraged to create a multi-scale modeling toolbox for structural biology problems. The additions proposed in this grant include integrating new crystallography refinement capabilities within Foldit, and adding new modes that allow much larger proteins to be handled in Foldit for cryo-EM. Together, these improvements will make Foldit a state-of-the-art structure solving suite for crystallography and cryo-EM. Significant updates in the results of the project can be found at https://www.fold.it.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.

结构生物学家的目标是以原子分辨率可视化生物分子，这是理解生物学各个方面的关键一步，包括疾病及其治疗。结构测定的主要实验方法，称为冷冻电子显微镜和X射线晶体学，依赖于将生物分子的原子拟合成三维“地图”，寻求与实验数据的一致性。这个拟合过程既费力又困难，但初步研究表明，公民科学家玩生物化学电脑游戏Foldit可以非常有效地完成这项任务。作为一个首屈一指的公民科学电脑游戏，Foldit自成立以来已经有超过60万人玩过。该项目旨在提高Foldit的能力，使科学家和公民科学家能够准确地构建不同类型和大小的生物结构。这种能力可以大大提高科学理解许多生物现象的基础的能力。除了这些科学效益外，该项目还使科学教育和整个社会受益。这一新功能将提高使用Foldit的教育选项的多样性和质量，使其成为科学界和社会之间的主要接口。Foldit是一个公民科学项目，用户可以帮助解决许多生物化学问题，包括蛋白质结构解决项目中的模型构建和真实的空间细化。早期的测试表明，这些企业生产高质量的晶体和低温EM结构，但还需要许多改进，使Foldit成为解决结构问题的首选。最近，新版本的Foldit已经推出，除了标准的公民科学Foldit谜题外，还可以由单个科学家或实验室小组使用。这些选项将被用来为结构生物学问题创建多尺度建模工具箱。在这项授权中提出的补充包括在Foldit中集成新的晶体学细化功能，并添加新的模式，允许在Foldit中处理更大的蛋白质进行冷冻EM。总之，这些改进将使Foldit成为晶体学和cryo-EM的最先进的结构解决套件。项目结果的重大更新可以在www.example.com上找到https://www.fold.it.This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。