Frequently Asked Questions

Browse this FAQ by topic, or feel free to search this page for for a keyword specific to your question!

General

What is Eterna?

Check out this page to learn more!

What is RNA?

Check out this page to learn more!

Is Eterna licensed under free licenses?

Eterna is free to play. All user content is submitted under the Creative Commons Attribution Non Commercial ShareAlike 3.0 License.

I don't have a strong science background. Will this game be over my head? Will I be any good?

Don't worry! Practically no knowledge of biology or chemistry is required to solve puzzles. As you spend time playing Eterna, you may find yourself learning quite a bit... and not even realizing it.

Help! I'm stuck on a puzzle! I have no idea what I'm doing!

Hang in there. The Eterna community is very friendly and eager to help. If you're feeling lost, post a screenshot and ask your question in chat. When you post a screenshot, make sure you enable numbering of nucleotides in your settings. It can make offering help much easier.

How do I take a screenshot?

Click the camera icon , available as the top sub-menu choice from the [3 lines] /Tools Menu Icon (on the bottom left of your screen) . You will be given an option of posting a link to the screenshot in chat. If you simply want to save a picture of a solution, click the link to the picture to open the image in a new browser tab.

How do I save puzzles in progress? And sometimes, why can't I view my old, auto-saved solutions?

Eterna has built-in auto-saving.

Unfinished Puzzles: Puzzles that you have started and leave but are not yet solved are automatically saved locally on your computer in flash cookies available to your web browser. Logging back in to the puzzle from the same web browser on the same computer should let you resume your work as the saved sequence reloads automatically.

Solved Puzzles get automatically stored on the Eterna server in the cloud and should then download for you to any browser on any computer when you open the puzzle.

Old solutions (those stored locally on your computer) have been known to disappear when players log on from different computers or if they delete their flash cookies. Certain browser settings and plugins may also be to blame. Occasionally, your saved solutions may be deleted for no apparent reason. This may indicate that the universe itself hates you. If you have a solution you want to be very sure is saved, Copy the current sequence to a text file and save it yourself. You can also take and save a screenshot.

Why can't RNA folding just be solved with computers?

RNA is a little more difficult than proteins when it comes to modeling for 3D. In proteins, there are basically only 2 torsion angles for backbone. For RNA, you need 7. (Nando)

Even strictly speaking of the puzzles, the fastest folding programs are still not as smart as those who have been playing for a few weeks or months, when it comes to puzzles larger than a few dozen nucleotides. (Hoglahoo)

Tools and Settings

Are there hotkeys in Eterna?

Yes. You can find a list here.

How do I access Tools and Settings?

Click the [3 lines] / Tools icon at the bottom left of your screen.

What can I do to speed up the game on my computer?

Enabling low performance mode can reduce the demand placed on your computer by the game's graphics. Some amount of lag is unavoidable when solving large puzzles on slower machines.

Puzzles

Why do base pairs pair?

Read an explanation here

Why does Guanine stabilize loops?

Are the puzzles based on real-life RNA?

99% of challenge puzzles, 0.01% of player puzzles (RedSpah)

Why are some puzzles called possible unsolvables?

Rumor has it that the developer puzzle authors were not sure whether they could be solved in Eterna's energy model and some, indeed, are not. (Hoglahoo)

Puzzle Designer

Why can't I make a puzzle longer than 400 nucleotides?

The game would take a lot longer to play, and it would likely be less enjoyable. You may notice a lag on larger puzzles. The cost of running an energy minimization increases with sequence length.

Why can't I require more than 1/3 GU pairs?

In the past, there was no limit on the GU restriction. The cap was imposed for a variety of reasons - among which are player enjoyment and relevance to naturally-occurring RNAs.

Can I save a design I'm working on and come back to it later?

The puzzle designer has an auto-save feature to a single saved slot. If you work on another puzzle in puzzle designer, it will overlay the single slot with your latest work. To keep puzzle designer work-in-progress from multiple puzzles, you can Copy key elements of your work to a text (notepad) file. Recommeended elements to include in the Save

(a) the dot-bracket notation of your structure
(b) the nucleotide sequence
(c) where applicable, a hyperlink to the original puzzle and the original puzzle name.

Note: If you have added a molecule, or marked bases using [Control] or [Alt], you may also wish to save a screenshot. When you want to restart work on your design, paste in the dot-bracket notation of your design, paste in your sequence, and recreate any other special elements from the screenshot.

Energy

What is free energy and why is it negative?

Main Article: Free Energy

In Eterna, free energy can be thought of as the energy released into the surroundings when a completely unfolded RNA molecule folds into its shape. A negative sign indicates that energy goes from the RNA into the surroundings when the RNA folds.

Do I need to make free energy as low as possible?

No. When you solve a puzzle, you design a sequence. A sequence can fold into a large number of shapes, each of which have different free energies. The goal of puzzle-solving is to create a sequence whose minimum free energy structure is equivalent to the target structure.

How is energy calculated in Eterna?

Eterna began with a single energy model, but now permits 4 different energy models, which calculate the energy in similar, but slightly different ways. The supported energy models are

Vienna 1.8.5 [the original and the Eterna default energy model]
Vienna 2.0 [tag is VRNA_2]
NuPACK [tag is NuPACK]
LinearFoldV [tag is LFV]

Puzzles using any of the non-default energy models show the non-default energy model tag in their title in square brackets, e.g. [VRNA_2], [NuPACK], [LFV]

In puzzle designer, you can switch between the energy models by clicking the [Venn Diagram] / [Select the Folding Engine Icon]. Warning: Switching energy models acts like a partial reset, removing your UNDO sequence.

Lab Submissions

Does very low or very high free energy ensure a successful design?

No. In nature, RNA does not always adopt its minimum free energy structure. Furthermore, the tools used to predict the minimum free energy structure are imperfect.

What is the optimal free energy?

No specific value of free energy is ideal. Most successful lab designs do not attempt achieve the maximum or minimum value of free energy possible for a given secondary structure.

Why shouldn't I use all GC pairs in a lab design?

GC-rich sequences are difficult to synthesize and prone to being caught in folding traps. Furthermore, the use of only one type of base pair increases the likelihood of undesired pairing.

Why shouldn't I use all AU or GU pairs in a lab design?

AU and GU pairs are weaker than GC pairs. Alone, they are unlikely to hold an RNA molecule in a specific structure. Furthermore, the use of only one type of base pair increases the likelihood of undesired pairing.

What is the optimal balance of AU, GU, and GC-pairs?

In general, designs with ~60% GC pairs tend to balance stability and ease of synthesis. This rule is not absolute, however. The frequency of GC pairs in some winning lab designs has exceded 70%.

How are my lab points calculated and what do they mean?

Read an explanation of the lab points here.

Dotplots and Melt Plots

What is a "melting plot" and what does it mean to "melt" RNA?

As temperature increases, hydrogen bonds (and thus, base pairs) are broken. In Eterna, the melting temperature can be thought of as the temperature at which there would be enough energy to pull the structure apart from its folded structure to a linear form. The process of increasing temperature to break base pairs and create a completely unpaired strand of RNA is called "melting". In Eterna, the melt plot shows the percentage of unpaired bases as a function of temperature.

How can I view the melting plot or dot plot?

Click the eye icon at the bottom of the screen while designing a lab submission.

What does a dotplot show?

A dotplot shows the probability of any two bases forming a base pair.

How do I read a dotplot?

The x and y axes of a dotplot represent individual nucleotides in the RNA molecule. Points within the dotplot represent interactions between bases. The point 4, 20 and the point 20, 4 both refer to the interaction between bases 4 and 20. A dotplot is divided diagonally into two triangles. The bottom left triangle shows only the base pairs present in the minimum free energy structure. The top right triangle shows the predicted probability of base pairs forming in nature. The darker the square in the top right triangle, the greater the probability of that base pair forming.

SHAPE Data

Why can a basepair in SHAPE data have both a blue and a yellow base, when blue means paired and yellow means unpaired?

Read Omei's explanation of why bases apear unpaired while their partner base appears paired.