Foldit for fun

When I first heard about a computer game based on folding proteins, I must admit, I was skeptical. How fun could it possibly be to manipulate a virtual protein for points? Well, after countless hours of first hand experimentation I've arrived at an answer: Very. The game is called Foldit, and luckily for one of the game's principle founders, David Baker, a biochemist at the University of Washington, thousands of others have come to the same conclusion. Baker hopes that Foldit -- launched two weeks ago -- will tap the human ability to solve puzzles, which he says surpasses computer capabilities. Eventually, Baker says, gamers may solve the structure of new proteins that may lead to cures for intractable human diseases such as HIV and malaria. The premise of Foldit is simple: See protein floating on screen. Drag parts of protein around to get it to the optimal energy state. The better the energy, the more points you get. But in order to make that happen, you must rearrange amino acid chains attached to the protein backbone, making sure they aren't hitting, or "clashing," each other and sending out spinning red stars on the screen. The game uses data from another home computer protein structure program -- called Rosetta@home. That software linkurl:Baker developed;http://www.the-scientist.com/2006/7/1/26/1/ to tap into home computers around the world while their owners weren't using them in order to compute complex protein structures. Based on algorithms in Rosetta, Foldit automatically fine-tunes human adjustments of proteins to optimal energy states. Ironically, the idea of Foldit came about nowhere near a computer screen. On a crisp day in October of 2006, Baker and a friend, David Salesin, went on a day-long hike into the backcountry of Mt. Rainier. Both were professors at University of Washington, but they worked in different departments and rarely talked about work. But over the course of the seven-hour hike, Baker explained to Salesin the Rosetta software. Baker told Salesin that some people whose computers were running Rosetta would Email Baker saying they would watch their computer working through various protein structures and wish they could tell the computer what to do --where to move a certain arm of amino acids, or bend the protein into a tighter fold. "If we could just let them grab the protein and do it themselves they'd be really excited about that," Salesin recalled the pair musing. The seeds for Foldit were planted. Soon Baker had assembled a team of computer programmers and even got advice from the designers of the video games Half-Life and Halo. So how do you play Foldit if you know nothing about protein structure? A set of tutorial puzzles helps you get the hang of clearing amino acid clashes and aligning protein backbones to create hydrogen bonding. I got through those relatively easily and was feeling pretty good about my protein structural sense. But as soon as I moved on to the competition puzzles, playing against other people, I couldn't get within 400 points of the top score. So I asked top-ranked Foldit player, "Ferzle," what the secret is. "If I had to sum up my winning strategy in one word I'd say 'perturbation,'" Ferzle, aka Charles Cusack, a computer scientist at Hope College in Michigan, told me. Cusack concentrates on clearing clashes and aligning backbones and then nudges things around until the points shoot up. "Some would call my strategy boring, I just keep retrying, but I think that's the best way." As Ferzle admits on his online profile, his knowledge of proteins ends at "you should eat it after exercising." It may be too soon to tell if any cures will come from Foldit players, but Baker seems confident that Foldit could be a new route to uncovering elusive protein structures. Already his team has been surprised by the response to the game, not to mention some of the high scores some players have achieved assembling known proteins. Soon, Baker's team hopes to introduce unsolved protein structures to the competitors and eventually, have players design proteins that might interact with pathogens like HIV. And that's where the real payoff could kick in. But regardless of how long Foldit stays popular, the game has already been slotted to replace some of Baker's current computer tools in his lab. They're developing an advanced version of the game to use in the lab for protein design. Science aside, once you get the hang of Foldit, tinkering with proteins can become downright addictive. So how much time does Ferzle devote to maintaining his top ranking? "It's scary. I've probably spent on average several hours a day for a couple months. Sometimes I'm on for six hours at a time." That's nothing, if you consider the countless hours linkurl:World of Warcraft;http://www.worldofwarcraft.com/index.xml and linkurl:Grand Theft Auto IV;http://www.rockstargames.com/IV/ junkies dedicate to their games. But for a guy who never plays computer games it's a hefty commitment. And how does his significant other feel about all that time spent at the computer? "That's the one good thing about being single," he said, "No one can yell at me for it."

Foldit for fun

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