ETERNA FAQ - By players for players

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.

1 Like

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?

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

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

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.

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

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.

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

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.

Q: What is Kcal?

A: Kcal is a measure of energy.

For more on free energy, go see here.

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.

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

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

Q: What is the purpose with puzzle solving?

A: The developer Tom gave a fine explanation here.

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

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.

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

@ 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.

@Hyphema, okay, thanks!

Good reading Eli!