ETERNA FAQ - By players for players

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This is the ingame player FAQ. Ask a question or help answering them. Devs are more than welcome to answer questions too.

Over time the best answers and questions will end up in this cleaned up version of the ETERNA FAQ.
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Eli Fisker

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Posted 7 years ago

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Eli Fisker

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Common question:

Q: How do I take a screenshot, when I'm stuck on a puzzle and needs help?

A: There is a symbol of a camera in the chat box, to the right side in the top. Click on the camera and say yes to post the picture in the chat.

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boganis

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Q: My chat window never completes loading, hence the camera symbol is not available. How can I make the chat work?
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Jeehyung Lee, Alum

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Hi boganis -

can you tell me which platform (windows/mac/linux), internet browser you are using and perhaps which version they are? It'll help us debug the problem.

we are sorry about the trouble.

EteRNA team
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boganis

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Hi, Jeehyung, OS: Windows 7 Professional (ver. 6.1 build: 7600), browser: Google Chrome (ver. 16.0.912.75 m).
I suspect it is the setup of my corporate McAfee SW or possibly blocking of computer ports - and the way the chat is implemented that could be part of the problem :)

However, I can't be the only one accessing EteRNA on a corporate laptop (in my leisure time) - thus I suspect that there are others that can't access the camera as well :)
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Eli Fisker

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Common question:

Q: Should I aim for highest or lowest free negative energy (kcal) in my lab design?

A: So what is the optimal kcal?

Free negative energy is needed for RNA to fold spontaneously, without adding of energy. Having just the right amount of free energy is the goal. That means not have too many GC-pairs or too many AU-pairs.

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

If you aim for lowest possible free energy, there will not be enough energy in the design to fold correct in nature. It will not have the power to stick together. A design with mostly AU pairs, means little free negative energy. The RNA will be too weak to stay in the structure you want it to form.

If you aim for the highest possible free negative energy, there is too much energy in the design for it to fold correct. A design can have so much free negative energy, that it get caught up in wrong folds. If you use too many GC-pairs, the design becomes like an energeticly black hole. Folds can't leave bad folds and the puzzle gets stuck on itself.

You can also imagine it like this:

GC-pairs are like electromagnets
AU-pairs and GU-pairs are like regular magnets – that rejects each other.

If you use mostly GC-pairs, they are very likely to get stuck somewhere wrong and then they won't let go again. Which means for the RNA to fold correct, will take like forever.

Watch the optimal % of GC-pairs in earlier winning lab puzzles, in a puzzletype that looks similar to the one you are working on.

(Thanks to Iroppy for mentioning gravitation when I was thinking mostly in electricity and magnetism related to all GC-designs.)
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Eli Fisker

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Correction on what I said earlier: "Free negative energy is needed for RNA to fold spontaneously, without adding of energy."

Here is an update. Quote from Berkeley Bio 1A - Fall 2006: General biology, lecture 33, minute 15.

"What a negative free energy means for a reaction is that there is no energy required for that reaction to occour. It is not really spontaneous."

Actually the teacher continues giving a real fine explanation on free energy and kinetics too. It made me understand things better. You can find the course at the above link. You might need to download ITunes to hear it.
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janelle

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Good reading Eli!
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Eli Fisker

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Here is the crewgenerated part of the ETERNA FAQ

Thanks to Mat for finding the link.
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Eli Fisker

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Common question:

Q: What is melting point?

A: 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 it folded structure to a linear form. (Matt Baumgartner)

For more information see Matt Baumgartner's post.
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Eli Fisker

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Common question:

Q: What can the meltplot tool be used for?

A: The meltplot tool can be used to avoid making one of the lowest scorings of designs. It can be used to predict a low score.

For more information on how to use it, read my post on the topic.
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Eli Fisker

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Common question:

Q: What is Free Energy?

A: When you are playing the puzzles in EteRNA, there is a box in the top left corner which displays the [free] energy of the current molecule. What that is a measure of is the potential energy of the molecule. (Quote Matt Baumgartner)

For more information see Matt Baumgartner's post.

Also see Ksteppe's Understanding free energy - using legos.
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Eli Fisker

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Common question:

Q: Is there a list of hot keys?

A: Yes, here.
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Eli Fisker

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Common question:

Q: What is dot plot or pairing propability plots?

A: See Jee's answer

For more about dot plot, see Lab guide for new players
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Eli Fisker

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Common question:

Q: What are the algorithm for EteRNA? What energy parameters and, energy model does it run on?

A: Link to paper is in this forum post

Thanks to Brourd for noticing the question and provide the answer.
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Eli Fisker

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Common question:

Q: How do I make a puzzle?

A: Here is a quick guide on How to use the puzzle maker.
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Eli Fisker

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Common question:

Q: How do I take a picture of a puzzles to send in a message, without publishing it in the chat?

A: Click the camera in the right top of the chat box once and wait.



Then this box appears



Choose the option, the underlined THIS



Then copy the link that appears together with the screenshot of your puzzle and save it somewhere.

Click no to posting the screenshot in chat.

Thanks to Starry for explaining this to me too, while answering to another player with this question.
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Eli Fisker

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Q: Why do I need to alternate (zigzag) AU-pairs in strings?

A: Because it enhances the stability of the string. Here is a post about Why AU-pairs should alternate in strings.
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Quasispecies

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I think we need a bit of jargon help. There is the jargon that players use, and the jargon that is used in literature.

Ideally, we should help players understand both. Can we make something that succinctly defines all of these terms? Can we provide lots of visual examples?
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Eli Fisker

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Hi Quasispecies!

Yes, you are quite right. Especially as we now move on to reading science papers, some term explanantion will be needed.

We need to identify the key terms we need to know to be able to work together on this babel like project.

I think my Eterna dictionary is only a temporary solution. The best would be if we could somehow get the key terms build into the WIKI, as it has a more intuitive structure than reading a dictionary. Other posibilities than the WIKI?

I'm thinking what about having some sort of list where we all can add words we don't understand but need to understand and then help each other with the explanation. And when a good explanation gets in, move it to the WIKI. We will need eterna crew to do some of the explanation too. And the biology students in here too. :)

Later when our discoveries get wider known, we will need to be able to make ourself understandable to the scientists.

Let me hear what the rest of you think. How can we solve this problem best possible?
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Eli Fisker

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Q: What is shape data and how do I read it?

A: Shape data is the chemical mapping of how the RNA bases are paired up after the RNA is synthesised. Yellow bases are the unpaired bases and blue base pairs are those that paired up. Click the yellow/blue picture of the design to see the shape data, when you are viewing the lab results. Shape data is a help when reading the results we get back from lab. For how to read the advanced shape data with continous colors, see this answer by Jee.
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Eli Fisker

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Q: Why do basepairs pair up?

A: The 3 basepairs AU, GU and GC each consists of one short base and one long base. The bases in a basepair is bound together by hydrogen bonds.

Hydrogen-bonds are typically weak attractions between two different molecules that holds those two molecules close together. (Definition Brightstorm.com) For a hydrogen bond to form, bases need to have a certain distance to each other.

The short bases consists of a single ringed base (green C and blue U) and are called pyrimidines.

The long bases are double ringed and are called purines (yellow A and red G)



I found the picture on this page.

To remember I chose to take the first letters in the short and long bases and connect them to something that I think I can remember. If it works, it works. :)

CUT - cut short

AG - A giant

Back to the pairing of bases. Picture that RNA folds up in helices like DNA. If you have two double ringed bases opposite each other, they will bump into each other and be too close to form proper hydrogen bonds. Two single rings would be too short to reach each other and thus not form bonds.

However a single ring and a double ring opposite each other have the perfect distance. It is the same in DNA, a short base opposite a longer base.

There is another reason that two long or short bases opposite each other won’t work, not thinking in the hydrogen bonds. The helix would be quite bumpy if basepairs of two short bases were next to a basepair of two long. It would screw with the biological machinery that have read and work along the line of basepairs in the helix of DNA.
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Eli Fisker

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Here is another regular question:

Why do G stabilizes loops?

If you haven’t read about why bases forms basepairs, you might want to see it as it holds the basis for understanding some of the following.

Answer: First here is what happens. A single G to the one side at the opening point in a loop, have a stabilising effect, if at the first spot in the loop across an A. This is called a G-A mismatch.

Drake explains mismatch like this:

When bases opposite to each other can not form a pair, it is called a mismatch. They result in unpaired bases, which form loops. The bigger the loop, the more energy it takes to hold together. Some mismatches are very efficient at splitting the strands from each other, encouraging loops to form. Loops starting with such mismatches take significantly less energy to hold.

Notice how the G-A mismatch lowers the energy in the loop. Less positive loops, means more stable loops.

Before


After


In a loop between two strings, you are allowed to place two G-A mismatches.



Now why do a G stabilize the loop? The G and A in a G-A mismatch are both are long bases. Those two are bad partners when in a helix, because they would bump into each other, being too close to each other to form proper bonds. But at the opening of a loop a mismatch can can work as stabilizer.

I asked Rhiju if G-A mismatch actually pair up - have hydrogen bonds between the G and A. He said, yes, they do.

It actually makes good sense. First they split the stack, making sure a loop opens up, then they have the perfect distance to each other, to actually form a pair with hydrogen bonds between them.

1-1 LOOPS

Something similar happens in 1-1 loops. G’s are long bases and two G's opposite each other, can't form a basepair in a string, as they would be bumb into each other and be to close to form hydrogen bonds. Instead they acts as splitters of a string, a mismatch.

I asked Rhiju if G-G in 1-1 loops forms hydrogen bond too and he says yes. Here two long bases (G's) helps split the string up, which creates a loop and then they keeps it in place. In a 1-1 loop they are suddenly perfectly distanced to each other to pair up and form hydrogen bonds. And so they add great strenght to the 1-1 loop and strings around it.





Notice the big jump in energy between before and after stabilizing. Negative energy in loops is good.

In bigger loops, a G-G mismatch won’t work. In loops bigger than 1-1, you will need a G-A mismatch.
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hoglahoo

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how does a G-G mismatch behave in lab? is it just like A-A as in the puzzles, where the tendency to form a loop is basically the same?
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Eli Fisker

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Sorry, Hogla, I am not sure how to answer this question.
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tox123

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What about C-A they don't link would they produce a mismatch?
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Hyphema

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@ tox, there are two ways to answer that question. On the puzzle , yes, C -A as well the other mismatches won't link and in many cases will alter the loops energy. In lab, mismatches like CA can actually "link" or pair together although they are weakly bonded. We know that RNA strands in real life have these non canonical pairings to some degree.
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tox123

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@Hyphema, okay, thanks!
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Eli Fisker

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Common question:

Q: Why are GU-pairs important in RNA?

A: GU-pairs have other electrical and chemical properties than the two regular Watson-Crick basepairs GC and AU.

Quasispecies said in chat sometime back:
The geometry of GU pairs is different than AU or GC, so GU pairs might help an RNA adopt a conformation that allows it to do something interesting.

Or as this abstract states it:

The G x U wobble base pair also has unique chemical, structural, dynamic and ligand-binding properties, which can only be partially mimicked by Watson-Crick base pairs or other mispairs. These features mark sites containing G x U pairs for recognition by proteins and other RNAs and allow the wobble pair to play essential functional roles in a remarkably wide range of biological processes.

The G x U wobble base pair. A fundamental building block of RNA structure crucial to RNA function in diverse biological systems
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Eli Fisker

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Dr. Drax added this beautiful little detail on where GU's are of use:

...tRNA, the chunks that translate from the three-NT sequences in mRNA to actual amino acids, often depend on GU bonds for their internal structure.
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Eli Fisker

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eternacac added following:

GU base pairs in RNA provide a complex array of hydrogen bond donors and acceptors creating a surface area for binding of proteinsand metal ions.

These base pair mismatches are recognition sites for proteins, metal ions and small molecules. (Jeffrey et al 1999; Blanchard et al 1998).

"Furthermore, the wobble pair GU is the most conserved in the group-Iintron contributing to the folded structure and base pairsof the type GA and AA provides additional stabilizationto the active core structure."

These are excerpts from this paper:

Non-Watson Crick base pairs might stabilize RNA structural motifs in ribozymes
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Eli Fisker

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Another usual question is:

Q: How long does it usually take for synthesis results to come back?

A: We are supposed to get results back from the first round before second round start, so we can use the results from first round to improve the second. And so on.

The puzzles are instant gratification, that is the game part of the game. The lab results are part of real world and thus prone to delay. That is the science part of the game. So be patient and don't despair.
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Eli Fisker

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Q: My puzzle won't finish submitting, what should I do?

A: I've had that happen a number of times. I just go back one page, open the puzzle again, deliberately flip a pair to cause a mismatch and then correct it. So far, that has worked everytime.

Answer by Wisdave
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Eli Fisker

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Q: How can I take screenshots?

A: You can use the ingame tool. This will give you a link to your picture, so you can share it in chat or in a message to another player.

You can also get a screenshot tool as a browser add on. Not all screenshot tools take pictures of all layers of the puzzles, like eg. the energy numbers. I use LightShot. It is for free and works with Firefox and Chrome.

If you know about other screenshot tools that work well with EteRNA, feel free to add them here.
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Eli Fisker

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Q: How can I hide the chat?

A: Click on "Players Online" in top of the chat box. This only gives a list of players and does not have any chatting going on. If you want it back again to follow the chat, just click "Chat".

You have to be in a puzzle to disable the chat.

Answer by Brourd
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Eli Fisker

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Q: What is Kcal?

A: Kcal is a measure of energy.

For more on free energy, go see here.
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Eli Fisker

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Q: Why is the free energy negative?

A: Our WIKI has a great explanation on why it is so.

Also see Ksteppe's Understanding Free energy - using legos.
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Eli Fisker

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Q: How do I see the solution I made for a puzzle after I've cleared it?

A: When you re-enter the puzzle you cleared, the cleared solution will be loaded by default. However, if you try to re-solve the puzzle, then it would show that autosave instead of cleared solution. In that case, just reset the puzzle and reload to bring up the cleared solution again.

Answer by Jee
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Eli Fisker

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Q: Do you get more points for a new solution resolve?

A: Unfortunately no : [ you only get points for the first time solving it.

Answer by Jee