On 2011, a group of players, carried away by healthy competition in a online game, they managed to decipher a problem that had been nagging virologists for a decade. In just three weeks, they figured out the three-dimensional structure of a HIV protein, considered a possible good candidate for the development of antiretroviral drugs. The game in question was called Foldit and its players even became part of the list of authors of the scientific study that was published later.
This story was one of the examples of citizen science and games that physics put Sara gil in a recent talk at the Science Outreach event. Without a doubt, it is a great example of all the good things that can come out if we mix both things.
But it did not end with HIV. In fact, they have since been introduced to the game Projects linked to the discovery of the structure of other proteins related to such notorious diseases as COVID-19 itself.
Why is protein structure so important?
Let’s imagine that we have all the parts of a clock mechanism. If we place them all in a row or even if we put them in the housing of the device, but without occupying specific places, the clock will not work.
If proteins lose their three-dimensional structure, they also lose their function
Something similar happens with proteins. They are made up of some basic blocks, called amino acids. Initially these are placed one after the other, as the information provided by the DNA is read. But for them to be functional it is necessary fold them so that they acquire a three-dimensional structure.
In fact, even once they are folded, if they are unfolded for any reason, they lose their function, reversibly or irreversibly. This is a process known as denaturation.
The problem is that it is not easy to know how a protein will fold; since, the bigger it is, the more possible conformations there will be. Today there are artificial intelligence algorithms such as Google AlphaFold, able to explore all those options and stick with the most likely ones. However, sometimes the human eye can be as infallible as a machine. Especially if there is a competition (or at least a collaboration between players) involved. This was the premise that led to the birth of an online game called Foldit.
Foldit, the online game to fold proteins
The online game Foldit is one of the oldest related to citizen science. Citizen science is about giving tools to the unskilled or amateur population to help scientists in searches that would otherwise take a long time. It is widely used, for example, in astronomy, to observe certain phenomena.
In this case, what was done was to create a collaborative puzzle game, whose objective was to fold proteins, following specific rules. These rules are related to the very procedures that proteins follow to fold naturally. For example, that the hydrophobic regions of amino acids, which do not like water, remain on the inside of the protein.
In search of HIV drugs
To fight the enemy, you must first know it. This warlike phrase makes a lot of sense in medicine, since to fight a pathogen it is very important to know it thoroughly.
Scientists had been trying to determine the structure of this HIV protein for 10 years
And that also happens to find out the folding of the proteins that compose it. Thus, much more effective drugs could be made against them.
For example, with HIV, among the preferred drug targets are proteins known as retroviral proteases. Specifically one, called M-PMV, was conceived at the beginning of this century as a possible weak point to which to direct drugs. But its three-dimensional structure was unknown.
Therefore, after ten years without being able to find it, its amino acid sequence was included among the Foldit challenges. And just three weeks later, users of the online game they had found her. More than 1,000 people were involved in the process that culminated in the publication of a study in Nature; in which, among its authors, were the players of Foldit. Given how important it is for scientists to be among the authors of a study, especially if it is published in a prestigious journal such as Nature, what these online players must have been a dream of. And if you want to try other proteins, you are in time to get into the game, because it is still active with other projects.