Fold.it : we are playing protein folding!

Anton Chugunov, "Biomolecule" based on ScienceDaily.

Scientists involved in predicting the spatial structure of proteins – as well as avid gamers – always lack the computing power of computers. Through their efforts, distributed networks have been functioning for several years, computers in which they calculate the properties of molecules in their free time from their main work. But the idea of the researchers does not stand still: now they are no longer claiming the computers of ordinary users, but theirs... heads!

A new computer game called FoldIt (in Russian, Fold it) turns the problem of predicting the three-dimensional structure of proteins into an exciting competition. The "training levels" built into the game will introduce the player to the "rules" – that is, with the physical laws that the polypeptide chain obeys, folding into a unique structure that is the key to the biological function of this protein, whether it is an Alzheimer's disease pathogen or a life-saving vaccine. After about 20 minutes of training, a newly minted gamer may have the feeling that he is really playing some kind of entertaining video game - although in fact his manipulations with a virtual molecule will serve for the benefit of real science, whose goals are much more serious than just entertaining idle players. The game is available for free on the website of the same name http://fold.it .

The game was created by researchers from University of Washington under the leadership of Professors of Computer Science and Engineering Zoran Popovic (Zoran Popovic) and David Salesin (David Salesin), as well as Professor of Biochemistry David Baker (David Baker). Game industry professionals also took part in the development of the game.

"Perhaps we will be able to change the way science is done, and even the way it is done," Popovits said in his speech at the Games for Health convention held in Baltimore. - "We strive to ensure that ordinary people who play a video game can one day become candidates for the Nobel Prize."

Proteins, of which there are more in the human body than the number of genes encoding them – due to posttranslational modifications or specific processes that result in unique antibodies – are the basis of life. And if the amino acid sequence of each of them is known, then the spatial structure of very many of them remains unraveled. Computer algorithms cannot sort through all possible variants of the structure of proteins "head-on" in order to choose the best solution from them: the limitation is the astronomical number of options that would have to be sorted out if the task was set in this way, and all computers on the planet would not have enough hundreds of years to solve it. In 2005, under the leadership of David Baker, the Rosetta@home distributed project was launched, combining the power of computers of those people who joined the project on a voluntary basis. But even the computers of 200,000 participants are not enough.

"There are too many variants [of the structure of the molecule] for computers to sort through them all," Baker says. - "Distributed projects like our Rosetta@home show good results on small proteins, but with an increase in the size of the simulated protein, the complexity of the problem increases non-linearly, and computer algorithms can no longer give the correct answer. However, people, using their intuition, can get the right answer much faster."

The FoldIt game, like the Rosetta@home distributed computing network, is based on the Rosetta "engine" designed to simulate the spatial packaging of proteins. However, the key feature of FoldIt compared to any other protein folding computer projects is that it requires something more from the participant than just the unused processor time of his personal computer or game console. FoldIt – and this is the novelty of the game – borrows from people their ability to solve three-dimensional puzzles, which is the task of "folding" another protein. The solution of each puzzle is accompanied by a sum of points directly related to the value of the potential energy of the protein in the conformation into which the player managed to collapse it.

Moreover, interestingly, the intuitive ability that allows someone to play FoldIt well (and the results of each "puzzle" are compared in real time via the Internet with other players) has practically nothing to do with the qualities needed by a real biologist. Baker says that his 13-year-old son folds proteins much faster than he does. (Here, obviously, we are talking about "training" levels, the answer to which is known, and, therefore, it is safe to say when the "assembly" process can be considered complete.) But others can work even faster. "I imagine a 12-year-old child prodigy somewhere in Indonesia, who in his head can imagine everything that we count here for weeks on the most powerful computers," Baker dreams.

Thus, the essence of this experiment is to find among non-scientists extraordinary talents endowed with a natural gift to "feel" the structure of proteins. "Some people manage, just by looking at the game and turning the molecule for just a couple of minutes, to get the maximum score," says Popovits. - "They can't really explain exactly what they do and how they do it, but somehow they still have this ability."

The game itself is something like a tetris of the XXI century – the entire screen is filled with a colored "snake", which can be twisted, folded and folded in different ways (using a computer mouse). A team of researchers from The University of Washington, including graduate students and undergraduates, spent more than a year trying to invent a design that would be both entertaining and scientifically correct. They had to solve many problems that developers of "ordinary" computer games do not have to face.

"Since we don't know the best result, we can't help the players and push them to the goal," Popovits explains the difficulties. Also, they could not assign any "bonus" to an individual move, for example, 1,000 points, because the points are directly related to the energy that the protein has in this conformation.

Over the past few weeks, about 1,000 players have been testing the system in the mode of working with well-known structures in order to establish a rating system and other subtleties of the gameplay. However, since very recently, proteins with an unknown structure have been added to the number of available "puzzles", "exposed" to the CASP competition (see the article "The Triumph of computer methods: predicting the structure of proteins". Thus, already now we are witnessing a unique battle of "professionals against amateurs", and no matter how it turns out that amateurs "by eye" give a better result than high-minded scientists!

The developers promise that after some time, players will be able to try on the role of not only a "predictor", but also a "designer", competing with each other in the virtual creation of enzymes with new functions, for example, capable of decomposing toxic waste or absorbing and assimilating carbon dioxide directly from the air. Computers – since they are not yet suitable for the role of creators – will take over the execution of simple operations, such as simple optimization of the molecule, allowing players to concentrate on really interesting "moves".

Ultimately, scientists plan to "grapple" with some of humanity's worst enemy, such as malaria or HIV, by offering players in their virtual protein universe to "invent" such a protein that would ideally block this or that pathogen and eventually defeat the disease. The most promising designs in each of the tasks will be "transferred from virtual to real" and synthesized in Baker's laboratory, where their activity will be tested on real biochemical systems. The most successful players are planned to be "rewarded" with thanks in scientific publications – as the most active users of the Rosetta@home network have already been thanked – and then, you see, more substantial prizes may begin to be distributed.

"In the long term, we would like to involve a significant part of the world's population in solving biomedical problems in a playful way and in the form of effective cooperation," Baker says. – "We are trying to use the potential of the brain of people around the world to intensify research in biology and medicine."

FoldIt includes common elements of most online games: the formation of user teams, chats, personal pages and profiles. After some time, the researchers plan to analyze the behavior of the most successful players in order, perhaps, to reveal hidden patterns in it. This information will be used for further development and improvement of the game.

The creation of this "research game" was funded by the Office of Advanced Research of the US Department of Defense (DARPA), the Howard Hughes Medical Institute, Microsoft and Adobe corporations; Nvidia and Intel specialists also participated in the development.

Portal "Eternal youth" http://vechnayamolodost.ru/16.05.2008