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Foldit Update: Playing Our Way To Better Drugs

Playing Games For Science

Following my prior posting G4H 2008: Serious Games for Key Discoveries in Molecular Science, here is a most interesting ARG approach to Foldit, explored by Star Spider at her Alternate Reality Existence Blog.

“We have seen creative crowd sourcing hard at work in games like
World Without Oil and Superstruct. We have witnessed grand emergent systems in online virtual spaces like World of Warcraft and Second Life. We have even seen a complex organic style virtual evolution simulation with Spore. And now we see the wisdom of the masses being put to work at something that could have both current and long term potential benefits for the progress of modern medicine and humankind as a whole. Foldit, is a game that has players all over the world competitively folding virtual proteins in unique ways and designing new proteins.”

"Knowing the structure of a protein is key to understanding how it works and to targeting it with drugs. The number of different ways even a small protein can fold is astronomical because there are so many degrees of freedom."

“The game was created by researchers at the Howard Hughes Medical Institute at the University of Washington and designed to be as simple and as fun as possible to make it both appealing and addictive. The more people fold, the more chance the researchers have of finding viable protein folds to target with drugs that could, ultimately, save lives.”

“As researchers and scientists find more practical applications for scientific simulation games in the real world we can expect to see more exciting developments like Foldit”.

Foldit Context

Via: ABC News - New Video Game Can Help Save Lives

One of the most important challenges in biology is identifying the fold of every protein. It's time-consuming and expensive.

To solve that, an innovative program at Stanford University is using ordinary personal computers around the world. 350,000 citizens have downloaded a little program called Folding@Home to donate spare computer time over the Internet-- even 30,000 Sony PlayStation. It's based on technology developed at UC Berkeley for the SETI at Home project to find extraterrestrial life.

Some other researchers are taking a different approach, recognizing that human intuition can be faster than a computer. The team (*) at the University of Washington turned the whole thing into a competitive online game.

(*)The game was developed by doctoral student Seth Cooper and postdoctoral researcher Adrien Treuille, and the undergraduate Janos Barbero all in computer science and engineering, working with Zoran Popović, a UW associate professor of computer science and engineering; David Baker, a UW professor of biochemistry and Howard Hughes Medical Institute investigator; and David Salesin, a UW professor of computer science and engineering. A number of CSE undergraduates contributed significantly to the game development process.

The research is funded by the Defense Advanced Research Projects Agency, Animation Research Labs, the Microsoft Corp. and Adobe Systems Inc., Howard Hughes Medical Institute and through fellowships at Nvidia Corp. and Intel Corp.

Solving Uncomputable Problems

Computer simulators calculate all possible protein shapes, but this is a mathematical problem so huge that all the computers in the world would take centuries to solve it. In 2005, Baker developed a project named Rosetta@home that taps into volunteers' computer time all around the world. But even 200,000 volunteers aren't enough.

"There are too many possibilities for the computer to go through every possible one," Baker said. "An approach like
Rosetta@home does well on small proteins, but as the protein gets bigger and bigger it gets harder and harder, and the computers often fail.

"People, using their intuition, might be able to home in on the right answer much more quickly."

Rosetta@home and Foldit both use the Rosetta protein-folding software.Foldit differs from recent human-computer interactive games that use humans' ability to recognize images or interpret text. Instead, Foldit capitalizes on people's natural 3-D problem-solving skills.

The intuitive skills that make someone good at playing Foldit are not necessarily the ones that make a top biologist. Baker says his 13-year-old son is faster at folding proteins than he is. Others may be even faster.

Eventually, the researchers hope to advance science by discovering protein-folding prodigies who have natural abilities to see proteins in 3-D.


The game looks like a 21st-century version of Tetris, with multicolored geometric snakes. Foldit turns protein folding into a competitive game.

Introductory levels teach the rules, which are the same laws of physics by which protein strands curl and twist into three-dimensional shapes -- key for biological mysteries ranging from Alzheimer's to vaccines. After about 20 minutes of training, people feel like they're playing a video game but are actually mouse-clicking in the name of medical science

"Some people are just able to look at the game and in less than two minutes, get to the top score," said Popović. "They can't even explain what they're doing, but somehow they're able to do it." "We don't know what the best result is, so we can't help people or hint people toward that goal," he explained.

Almost 1,000 players have tested the system, playing informal challenges using proteins with known shapes.

Starting November, Foldit has been expanded into a new game that essentially challenges players to design new proteins from scratch. Foldit gamers face off against research groups around the world in a major protein-structure competition. In December, puzzles for growing and moulding synthetic proteins that bind specifically to a virus have gone live.

Computers alone cannot design a protein from scratch. The game lets the computer help out when it's a simple optimization problem -- the same way that computer solitaire sometimes moves the cards to clean up the table -- letting the player concentrate on interesting moves.

Eventually, the researchers hope to present a medical nemesis, such as HIV or malaria, and challenge players to devise a protein with just the right shape to lock into the virus and deactivate it. Winning protein designs will be synthesized in Baker's lab and tested in petri dishes. High-scoring players will be credited in scientific publications the way that top Rosetta@home contributors already are credited for their computer time.

"Long-term, I'm hoping that we can get a significant fraction of the world's population engaged in solving critical problems in world health, and doing it collaboratively and successfully through the game," Baker said. "We're trying to use the brain power of people all around the world to advance biomedical research."

Foldit includes elements of multiplayer games in which people can team up, chat with other players and create online profiles. Over time the researchers will analyze people's moves to see how the top players solve puzzles. This information will be fed back into the game's design so the game's tools and format can evolve.