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.

结构生物学家的目的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的关键步骤，包括疾病及其治愈方法。用于确定结构的主要实验方法，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到三维“地图”中，以寻求与实验数据一致的一致。这个拟合过程是实验室和困难的，但是初步研究表明，这项任务可以由公民科学计算机游戏折叠非常有效地执行。作为一款主要的公民科学计算机游戏，自成立以来，Foldit已经有超过60万人玩。该项目旨在提高折叠功能，以使科学家和公民科学家能够准确地建立不同类型和大小的生物结构。能力可以强烈提高科学理解许多生物学现象的基础的能力。除了这些科学的好处外，该项目还受益于科学教育和整个社会。这种新功能将使用折叠式提高教育选择的多样性和质量，从而将其作为科学界与社会之间的主要界面提高。对于解决晶体和冷冻EM结构的方法，不断需要改进。 Foldit是一个公民科学项目，用户在该项目中协助许多生物化学问题，包括模型建设和蛋白质结构解决项目中的真实空间改进。早期测试表明，这些合资企业会产生高质量的晶体和冷冻EM结构，但是需要进行许多改进才能使折叠问题成为解决结构解决问题的首选。最近，除了标准的公民科学折叠难题外，还引入了新版本的折叠版本。这些选项将被利用，以创建用于结构生物学问题的多尺度建模工具箱。该赠款中提出的增加包括在折叠中整合新的晶体学改进功能，并添加新模式，这些模式允许在折叠中处理更大的蛋白质，以用于冷冻EM。这些改进将使折叠术成为解决晶体学和冷冻EM的最先进结构套件。该项目结果的重大更新可以在https：//www.fold.it.it.t.t.ins奖中找到反映NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响审查标准来评估，被视为珍贵的支持。