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 “mapsâ€, 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.
