Collaborative Research: CIBR: Incorporating Crystallography and Cryo-EM tools into Foldit

合作研究：CIBR：将晶体学和冷冻电镜工具纳入 Foldit

• 批准号: 2051282
• 负责人: Firas Khatib
• 金额: $ 55.76万
• 依托单位: University of Massachusetts, Dartmouth
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2051282&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在原子分辨率下可视化生物分子，这是理解生物学各个方面（包括疾病及其治疗）的关键一步。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。依靠将生物分子中的原子拟合成三维“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，通过玩生物化学计算机的公民科学家可以非常有效地完成这项任务。游戏 Foldit。作为一款顶级的公民科学计算机游戏，Foldit 自推出以来已有超过 600,000 人玩过。该项目旨在提高 Foldit 的功能，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。这种能力可以极大地提高科学理解许多生物现象的基础的能力。除了这些科学益处之外，该项目还有益于科学教育和整个社会，这种新能力将提高教育选择的多样性和质量。 Foldit，将其改进为科学界和社会之间的主要界面。人们一直需要改进解决晶体和冷冻电镜结构的方法，Foldit 是一个公民科学项目，用户可以在其中帮助解决许多生物化学问题，包括模型。早期测试表明，这些企业可以生产高质量的晶体和冷冻电镜结构，但需要进行许多改进才能使 Foldit 成为解决结构问题的首选。折叠已经除了标准的公民科学 Foldit 谜题外，该项目还介绍了可供单个科学家或实验室小组使用的功能，这些选项将用于创建结构生物学问题的多尺度建模工具箱。本次拨款中提出的补充包括整合新的晶体学细化。 Foldit 中的功能，并添加新的模式，允许在 Foldit 中处理更大的蛋白质以进行冷冻电镜，这些改进将使 Foldit 成为晶体学和冷冻电镜的最先进的结构求解套件。该项目结果的重要更新可在 https://www.fold.it 上找到。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。