20th September 2011

Video gamers solve microbiology puzzle

The Telegraph, 20 September 2011

Players of a 3D online computer game have provided the answer to a protein structure puzzle that could lead to new anti-retrovirus drugs.

Scientists had been struggling to map the structure of M-PMV, a protein involved in a virus that causes a form of simian Aids, in an experiment called CASP9. The search, in that experiment and others, had been going on for more than a decade. The solution was not found by a laboratory but the players of an online puzzle game.
Foldit takes the best known models of proteins and offers them to game players, many of whom have no background in science at all. Armed with a set of tools to play with the model, the aim is to produce a version that is as stable as possible, with no molecules clashing with any others and low internal energy.

To solve the puzzle it is not necessary to know what the parts of the model represent, only how they work within the game. Each protein becomes a three-dimensional brainteaser that could be purely abstract but in fact represents a particle that occurs in the real world.

Players manipulate the model within the game, stretching bonds between sheets, tucking stray molecules into free spaces and eliminating voids. They gain points by producing a stable solution and can form teams that work together, combining the successful parts of their individual solutions.
In CASP9’s case, they were initially hampered by the computer modelling that had already taken place. Trapped within the automatic analysis’s best guess, they were unable to make the radical moves that eventually led to the correct answer. Once the puzzle had been re-submitted to the gamers with a greater scope for experimentation, a group calling themselves the Foldit Contenders found the correct path within ten days. A user calling herself mimi made the final modification, but she was keen to stress that it was a collective effort.

She told MSNBC: ‘I had looked at the structure of the options we were presented with and identified that it would be better if the ‘flap’ could be made to sit closer to the body of the protein – one of the basic rules of folding is to make the protein as compact as possible – but when I tried this with my solo solution, I couldn’t get it to work. However, when I applied the same approach to the evolved solution that had been worked on by other team members, I was able to get it to tuck in, and that proved to be the answer to the structure. I believe that it was the changes made by my colleagues that enabled mine to work, so it was very much a team effort.’
The paper announcing the solving of the protein in the journal Nature Structural and Molecular Biology credits Foldit Contenders Group rather than individual players and mimi has asked that only her Foldit name should be used in press reports.

X-ray crystallography was used to confirm the solution. It is hoped that the new understanding of the protein can now be used in the design of anti-retroviral treatments, including anti-HIV drugs.