One of the great unsolved problems in biology is how proteins fold.  A protein is a chain of amino acids (determined by your DNA) which coils itself in some complicated configuration.  For example,

Protein before and after folding.

The twisted up configuration of the protein plays an important role in how it functions.  Diseases such as mad cow disease are caused by bad folding.  In principle, the string of amino acids in a protein determines how it will fold up.  In practice, it is tremendously difficult to predict the shape of a folded protein if you’re only given the amino acid string.  The math involved uses knot theory and other aspects of topology along with algorithms and minimization problems.

There is computer programs like Fold@home which uses massive computational power to determine the folding of proteins.  But the possible number of configurations is staggering and it turns out computers aren’t great at 3D folding problems.

On the other hand, humans have being working in 3D all their lives.  This led to a different approach to the problem, a computer game called Foldit.  The (in retrospect obvious) idea is that protein folding is a puzzle and if you make it an online game where people get points for correctly folding proteins, then people will play!  Here’s what the game looks like:

We haven’t played it at Math Club HQ, but apparently it’s great fun if you like puzzles.  Here’s a cool video talking about Foldit:

Not only is it fun, it turns out to work!  Not only are people good at folding proteins, they have successfully solved a real-world protein folding problem!  See the full article here.  The problem was to find the folding of a protein involved in M-PMV, a simian AIDS–causing monkey virus:

The most important problem solved by Foldit players to date came after CASP9 and involves the Mason-Pfizer monkey virus (M-PMV) retroviral protease….  despite the availability of several crystal forms, researchers have for over a decade been unable to solve the structure by molecular replacement (MR) using either homodimer-derived models or an NMR structure of the protein monomer…. we challenged Foldit players to build accurate models of M-PMV PR starting from the NMR coordinates…. When the 3-week competition concluded, we screened the top-scoring Foldit models using Phaser to determine whether any were of sufficient quality for MR. Remarkably, despite the complete failure of all previous approaches, several solutions by the Foldit Contenders Group produced phase estimates that were good enough to allow a rapid solution of the crystal structure.

Next time your roommate gives you a hard time for “wasting” all your time playing computer games, you can tell them that you’re curing diseases!


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