Using the computer game, “Foldit,” nonexpert citizen scientists designed new proteins whose structures, verified at the Advanced Light Source (ALS), were equivalent in quality to and more structurally diverse than computer-generated designs.
Proteins constitute the biomachinery—the cellular gears and levers—that make our bodies work. When this machinery is running smoothly, nutrients get absorbed, cells regenerate, and so on. When the machinery breaks down, the tools needed to fix the problem (i.e. drug molecules) are often proteins themselves.
Until recently, the pool of proteins available for such therapeutic purposes was limited to those found in nature. But natural proteins represent a small subset of all the possible ways to link 20 amino acids—the basic building blocks of all proteins—into chains hundreds, even thousands, of units long. On top of this, there are countless ways in which any given protein chain can fold—a key aspect of functionality.
In the last 20 years, “de novo” protein design (from scratch as opposed to starting with a known protein) has taken off, promising cheap and effective drugs with fewer side effects. But given the huge number of possibilities available, scientists are limited in their ability to fully explore this vast “protein space.”
Image: The user interface of Foldit, a free online computer game developed to crowdsource problems in protein modeling. (a) The Foldit score: better models yield higher scores. (b) The design palette allows players to change the amino acids in the protein chain. (c) The “pull” tool allows players to manipulate the 3D structure of the model. (d) The “undo” graph tracks the score as a model is developed and allows players to backtrack. (e) Additional tool selections.