User talk:ElNando888/Blog/SCOR

Before I continue with my musings about this strange dinucleotide animal, I'd like to invite the readers to share their thoughts. What do you think is going on here ? I have my own theories, but I'd really like to know what are your points of view about this.

Thanks for participating.

-- ElNando888 (talk) 16:05, 22 April 2013 (UTC)Reply[reply]

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Wow, that was alot more response than I expected. I am defintely going to try out Chimera when I have a bit more time. Thank you. And it makes sense, it's up to us to determine which sequences work on our own, and that can be a bit of work on it's own. As far as the MFE/Native structures, is the UG too weak a bond to hold a loop like that(or of that energy.. size.. ?), and is the -1 to -2.5 energy difference in the quads on the lower side of the loop too great to keep stability... or, does that explain why native reverts to a higher Kcal? I look forward to the next installment : ) - wilf.

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Well, I think there are two ways to approach the problem. Either the model that EteRNA uses overestimates the stability of the MFE, or it underestimates the native fold. I believe, the answers are more likely to be found in the second option. When you'll have Chimera running, try to play around with the molecule, the screenshots I'm offering are nice, but they can't replace the visual 3D exploration... Still, did someone notice any features or particularities in these 3D renderings I posted ?

-- ElNando888 (talk) 01:36, 23 April 2013 (UTC)Reply[reply]

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I only just downloaded Chimera, and am working through the quickstart guide you wrote... in the 3d images you posted, U5 and A6 look very parallel to each other, it seems their sides line up well. Did you mean the spatial relation of U5 / A6 to each other, or to surrounding bases... They look organized well in the structure(?). Tha's all I see so far...

-wilf

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Splendid :) Yes, it's precisely those two bases. But they are more than just parallel, they actually are co-planar. And very close to each other, of course. And you know what happens when nucleobases are co-planar and close ? Of course, you do know, they form hydrogen bonds. In other words, they pair.

Now if you think about it, where did you find this sequence and 3D structure in the first place ? In a database, classified as a "dinucleotide platform". What does that mean ? "dinucleotide" is clear and simple, we're talking about two bases. But if it's just a normal pair, canonical or not, why would they invent this "platform" thing ? Yes, because it's a very unusual pairing, which occurs between neighboring bases on the same side of the chain.

So, coming back to the 2D native structure, EteRNA (and probably all other models) is missing a couple hydrogen bonds from a "weird" pair, which should make for a small contribution to stability. But that's not all of it, I think. I edited the second 3D shot to give you a hint.

superposed bases

What does this inspire you ?

-- ElNando888 (talk) 21:13, 23 April 2013 (UTC)Reply[reply]

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OK, looks like a triloop to me w/ GC closing, or a 1 NT bulge. Since this is in the middle of the structure, I'll go with 1 NT bulge.

-wilf

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Yes, a 1 nt bulge. It may seem a little far fetched, but to me, this suggests that this 2-0 bulge that we can see in the native structure may actually work nearly as good as a 1-0 bulge. What difference would that make ? Just take the native structure in the puzzle editor again, and simply remove A6. What do you see in the energies now ? Wouldn't it at least partially explain that EteRNA underestimates the FE of the native structure ?

-- ElNando888 (talk) 00:37, 24 April 2013 (UTC)Reply[reply]

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Just coming back a minute on what I was saying earlier : I believe that due to the fact that U5 and A6 are in the same plane, things in this 2-0 bulge are working as if this would be a 1-0 bulge. This may be a little over-optimistic, but please bear with me until the end :)

There is actually another section of the 3D rendering that I didn't present until now, in the hope that it would be noticed by someone else.

This is the area around the 1-0 bulge at A17. On the left, the "normal" view, which is difficult to "decode". Don't ask me how I got the picture on the right, but after toying for a while with some menu options, I managed to make the backbone and the sugars invisible, leaving only the bases. And I believe, the result is quite eloquent.

Observe the placement of A17. Yes, that's an even weirder combo, A18 actually pairs with U8 and A17. That's called a "base triple"

Observe the alignment of the vertical axis, globally. See a bent anywhere ? Well, to me, just like earlier, this suggests that, because A17 is in the same plane as the U8-A18 pair, this 1-0 bulge may very well work just like a... 0-0 bulge.

Now, what does EteRNA think of the native structure without A6 and without A17 ?

Now, if you guys have a better explanation for why the native structure is preferred over the MFE, I'm all ears :)