October 05, 2016
Computer
gaming is now a regular part of life for many people. Beyond just being
entertaining, though, it can be a very useful tool in education and in science.
If
people spent just a fraction of their play time solving real-life scientific
puzzles – by playing science-based video games – what new knowledge might we
uncover? Many games aim to take academic advantage of the countless hours
people spend gaming each day. In the field of biochemistry alone, there are
several, including the popular game Foldit.
In
Foldit, players attempt to figure out the detailed three-dimensional structure
of proteins by manipulating a simulated protein displayed on their computer
screen. They must observe various constraints based in the real world, such as
the order of amino acids and how close to each other their biochemical
properties permit them to get. In academic research, these tasks are typically
performed by trained experts.
Thousands
of people – with and without scientific training – play Foldit regularly. Sure,
they’re having fun, but are they really contributing to science in ways experts
don’t already? To answer this question – to find out how much we can learn by
having nonexperts play scientific games – we recently set up a Foldit
competition between gamers, undergraduate students and professional scientists.
The amateur gamers did better than the professional scientists managed
using their usual software.
This
suggests that scientific games like Foldit can truly be valuable resources for
biochemistry research while simultaneously providing enjoyable recreation. More
widely, it shows the promise that crowdsourcing to gamers (or “gamesourcing”) could offer to many fields
of study.
Looking closely at proteins
Proteins
perform basically all the microscopic tasks necessary to keep organisms alive
and healthy, from building cell walls to fighting disease. By
seeing the proteins up close, biochemists can much better understand life
itself.
Understanding
how proteins fold is also critical because if they don’t fold properly, the
proteins can’t do their tasks in the cell. Worse, some proteins, when
improperly folded, can cause debilitating diseases, such as
Alzheimer’s, Parkinson’s and ALS.
Taking pictures of proteins
First,
by analyzing the DNA that tells cells how to make a given protein, we know the
sequence of amino acids that makes up the protein. But that doesn’t tell us
what shape the protein takes.
An
electron density map of a protein, generated by X-ray crystallography. Scott
Horowitz, CC BY-ND
To
get a picture of the three-dimensional structure, we use a technique called X-ray
crystallography. This allows us to see objects that are only
nanometers in size. By taking X-rays of the protein from multiple angles, we
can construct a digital 3D model (called an electron density map) with the
rough outlines of the protein’s actual shape. Then it’s up to the scientist to
determine how the sequence of amino acids folds together in a way that both
fits the electron density map and also is biochemically sound.
Although
this process isn’t easy, many crystallographers think that it is the most fun
part of crystallography because it is like solving a three-dimensional jigsaw
puzzle.
An
electron density map of a protein with the protein threaded through the map,
revealing how the protein folds. Scott Horowitz, CC BY-ND
An addictive puzzle
The
competition, and its result, were the culmination of several years of improving
biochemistry education by showing how it can be like gaming. We teach an
undergraduate class that includes a section on how biochemists can determine
what proteins look like.
When
we gave an electron density map to our students and had them move the amino
acids around with a mouse and keyboard and fold the protein into the map,
students loved it – some so much they found themselves ignoring their other
homework in favor of our puzzle. As the students worked on the assignment, we
found the questions they raised became increasingly sophisticated, delving
deeply into the underlying biochemistry of the protein.
In
the end, 10 percent of the class actually managed to improve on the structure
that had been previously solved by professional crystallographers. They tweaked
the pieces so they fit better than the professionals had been able to. Most
likely, since 60 students were working on it separately, some of them managed
to fix a number of small errors that had been missed by the original
crystallographers. This outcome reminded us of the game Foldit.
From the classroom to the game lab
Like
crystallographers, Foldit players manipulate amino acids to figure out a
protein’s structure based on their own puzzle-solving intuition. But rather
than one trained expert working alone, thousands of nonscientist players worldwide
get involved. They’re devoted gamers looking for challenging puzzles and
willing to use their gaming skills for a good
Cause.
Foldit’s
developers had just finished a new version of the game providing puzzles based
on three-dimensional crystallographic electron density maps. They were ready to
see how players would do.
We
gave students a new crystallography assignment, and told them they would be
competing against Foldit players to produce the best structure. We also got two
trained crystallographers to compete using the software they’d be familiar
with, as well as several automated software packages that crystallographers
often use. The race was on!
Amateurs outdo professionals
The
students attacked the assignment vigorously, as did the Foldit players. As
before, the students learned how proteins are put together through shaping
these protein structures by hand. Moreover, both groups appeared to take pride
in their role in pioneering new science.
At
the end of the competition, we analyzed all the structures from all the
participants. We calculated statistics about the competing structures that told
us how correct each participant was in their solution to the puzzle. The
results ranged from very poor structures that didn’t fit the map at all to
exemplary solutions.
The
best structure came from a group of nine Foldit players who worked
collaboratively to come up with a spectacular protein structure. Their
structure turned out to be even better than the structures from the two trained
professionals.
Students
and Foldit players alike were eager to master difficult concepts because it was
fun. The results they came up with gave us useful scientific results that can
really improve biochemistry.
There
are many other games along similar lines, including the “Discovery”
mini-game in the massively multiplayer online role-playing game “Eve Online,”
which helps build the Human Protein Atlas, and Eterna,
which tries to decipher how RNA molecules fold themselves up. If educators
incorporate scientific games into their curricula potentially as early as
middle school, they are likely to find students becoming highly motivated to
learn at a very deep level while having a good time. We encourage game
designers and scientists to work together more to create games with purpose,
and gamers of the world should play more to bolster the scientific process.
https://theconversation.com/play-video-games-advance-science-65688
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