Five years ago, I wrote about the advent of a new interactive online video game, then called EteRNA (and now simply Eterna), that lets non-scientist players design complex biomolecules with real-life applications. Players do this by following simple rules that dictate whether a potential structure is going to be physically stable – that is, whether the molecule, once built and plunked into the environment of a living cell, would actually retain its desired shape.
The biomolecules in question were made of an amazingly flexible substance called RNA, whose biological activity is hugely determined by the exact shape that the RNA molecule assumes.
Eterna now boasts more than 100,000 registered players, Stanford RNA biochemist and the game’s co-inventor, Rhiju Das, PhD, told me – and that’s just the number who’ve achieved enough familiarity with the game to qualify.
The frosting on the cake: The consortium of Eterna players have just had their first paper published in the peer-reviewed Journal of Molecular Biology, possibly marking the first time since the days of Benjamin Franklin that work led by non-credentialed “citizen scientists” has appeared in such a format. As I wrote in our news release:
The paper describes a new set of rules, derived intuitively by players of a video game called Eterna, for determining the difficulty of designing desired structures composed of RNA molecules. Unlike previous crowdsourcing efforts for which scientific experts have reached out to online gamers, the gamers themselves took the lead in this paper.
Far less famous than its close cousin DNA, RNA probably entered the evolutionary arena long before DNA came on the scene. Like DNA, RNA molecules are strands consisting of four different chemical building blocks hooked together in sometimes-stultifyingly lengthy sequences.
Biochemically quite similar to DNA, RNA is structurally far more flexible. That’s largely because whereas DNA is famously double-stranded, a typical RNA molecule travels as a free-floating single strand. Without the need to be constantly embracing a partner strand, it is thus a rather floppy, string-like molecule.
Nonetheless, the same electrochemical affinities (specifically, between opposing strands’ constituent chemical building blocks) that generate and maintain DNA’s rigid double helix are at work in an RNA molecule, albeit in a more fleeting form: Small sequences of chemical building blocks along the molecule can find themselves attracted to sequences elsewhere on the same strand, causing the molecule to double back on itself and fold into shapes featuring pinched double-stranded sections, known as “stems,” alternating with “bulges,” “zigzags,” “loops,” “hairpins” and “hinges.”
The Eterna players’ most counterintuitive finding, among several that have been confirmed by Stanford supercomputers: The more symmetrical and visually pleasing the desired shape of an RNA molecule, the more difficult it’s going to be to design.
Previously: Gamers: The new face of scientific research?, Mob science: Video game, EteRNA, lets amateurs advance RNA research and Paramecia PacMan: Researchers create video games using living organisms
Photo of Rhiju Das by Norbert von der Groeben; image from the game by Vineet Kosaraju