Recently I came across Fold It. It is a testament to the power of games and gamification and what they can do for the world.
Gamification is all about engagement and using mechanics to create intrinsically motivating experiences. In fact I became passionate about gamification when I realized what felt like ten minutes playing a game was actually a couple of hours. The immersion that games provide is truly something special. Something that I call a superpower. Harnessing that something special and applying it to something is else is catching lightning in a bottle and Fold It has done just that. Fold It is a game that is changing the world one fold at a time.
Solve it with science
Here’s a quick glance at what it’s like to play Foldit:
What you saw in the video was a 3D diagram of an actual protein being folded by someone (potentially in their undies) playing a videogame.
So what are proteins and why do they fold? Here’s a cartoon explanation in five easy steps:
- This is DNA, think of it like a blueprint for a machine. Just like a car has a blueprint, so do proteins in your body. The blueprint is made up of tiny molecules called nucleotides that are ordered along the inside of the DNA molecule.
- First the blueprint gets copied. Specialized proteins or cellular machines come in and copy the DNA into mRNA. One of the main proteins is called RNA polymerase. Think of it as making a copy of the blueprint on carbon paper.
- Then the blueprint gets read. The mRNA leaves the nucleus of the cell and is read by a cellular machine called a ribosome. The ribosome is like a car assembly line, it reads the blueprints and assembles the parts of the machine. Proteins are made up of molecules called amino acids, they’re like car parts. Amino acids are brought to the ribosome by tRNA molecules.
- The protein folds into a functional form. This is where the metaphor gets complicated; imagine that instead of assembling cars into their finished form all the parts were attached to one long string with magnets at special spots. All you would need to do to assemble the car is fold the string up the right way with all the correct magnets touching to hold it together. That’s kind of how proteins assemble themselves; they are long strings of amino acids that can attract and repulse each other. Based on the order they are in the attractive and repulsive forces can create a lot of different shapes and structures.
Here’s a neat video showing what I mean:
- The protein is complete. Once a protein has folded into its final form proteins can do all kinds of things based on their structure, they can break things apart, they can put things together, and all kinds of other jobs. Remember just like real machines, there can be many different proteins for many different jobs.
Okay science lesson over.
Just keep folding
For a while computers were tasked with folding these proteins. The problem was that the computers weren’t very good at solving for the proteins because they lacked high level problem solving. For example, when we solve a puzzle we can see that two pieces fit before we even try to fit them together. Computers do not have this ability. So the creators of Fold It decided that the task might be better in the hands of humans. And indeed humans were actually better at solving for proteins than the computers. So they decided to make it public by creating the game Fold It.
The power of gamification
A puzzle based game about folding proteins, Fold It looked to harness the power of games for the good of science. Humans were able to do high level special fitting while allowing the computers to take care of the low level quantitative stuff. Players are given a score as they fold the protein. Better score if your protein is better folded. Always getting feedback on how well they’re doing with their folding. Also a leaderboard of players high scores on proteins every in the world is working on. They even held weekly protein folding competitions for players to grab the highest score. People who solved it didn’t have any previous background in biochemistry. Main motivation for playing the game was Purpose, were doing something that might help science, help fight disease.
Foldit is a game-changing game, gamifying the process of scientific discovery. The biggest accomplishment to date was when gamers solved the structure of an important protein found in the HIV virus. The protein is called M-PMV retroviral protease or HIV-1 protease1. Without this protein the HIV virus cannot create infectious self-copies called virions2. Understanding the structure of this protein is very important because it can help lead to the creation of drugs to target and disrupt HIV-1 protease’s biological action1.
Here’s the crazy thing though, proteins can be hundreds of amino acids long with thousands of possible ways they could fold3. While it is easy (relatively speaking) to find out the order of a protein, this makes it very difficult to know the structure of how it folds. This is where foldit has really been innovative because you get more points for making stronger proteins.
A ‘stronger’ protein is based on three things in the game: it being compact and not having empty spaces, by hiding amino acids that don’t like water on the inside of the protein, and by not forcing amino acids too close together4.
Based on these criteria gamers who score highly in game are likely to have a realistic protein structure. This is useful because once researchers have an idea of a protein’s structure, they can test known drugs that work on proteins like it. This is how foldit solving the HIV-1 protease structure has led to opportunities for HIV drug development. The game is open to all who would like to play, who knows maybe you might solve the next big protein puzzle. You can download the game and start playing at http://fold.it/portal/.