Prof. David Baker, a protein research scientist at the University of Washington, founded the Foldit project. Seth Cooper was the lead game designer. Before starting the project, Baker and his laboratory coworkers relied on another research project named Rosetta to predict the native structures of various proteins using special computer protein structure prediction algorithms. Rosetta was eventually extended to use the power of distributed computing: The Rosetta@home program was made available for public download, and displayed its protein-folding progress as a screensaver. Its results were sent to a central server for verification.
Some Rosetta@home users became frustrated when they saw ways to solve protein structures, but could not interact with the program. Hoping that humans could improve the computers' attempts to solve protein structures, Baker approached David Salesin and Zoran Popović, computer science professors at the same university, to help conceptualize and build an interactive program, a video game, that would appeal to the public and help efforts to find native protein structures.