Drop in melt plot

Has anyone seen a melt plot that drops at some point rather than always rising or staying flat?

If you’re interested, look at my submission for lab #14, wisdave14. I’ve never seen that before, but maybe others have.

Hi Wisdave.

I have seen it before. (Unfortunately I don’t remember where) It is rather rare though. And when it did turn up it caused confusion. I don’t know what is causing it. Anyone who have an idea or remember the other designs with drop in the melt plot, please post a note here.

I think the explanation could be actually quite simple : for a given sequence, considering all its possible misfolds, there is a chance that one misfold with less pairs actually has a better free energy than another with more pairs.

If I remember correctly, the melt plot is about the number of paired bases still present, in percentage of the length of the sequence. As the temperature increases, the sequence “evolves” from the MFE to structures which were more unstable at 37C. On this “path”, it may encounter shapes with more or less pairs…

Another example of drops could actually be observed in lab switches, specially in those where the state 2 (bound) is very close from the state 1 (unbound) and state 2 has more pairs than state 1. Perfect example: Hand & Finger (19 and 23). My explanation for the V shape start of the melt-plot in some designs, was simply that very quickly with the temperature raise, the sequence would adopt state 2 shape (without binding molecule) and with 23 pairs instead of 19, causing a drop in the plot

I had quite a few of them a long time ago.

I agree with what nando says, but I also think the effect partly comes by some pairs unbinding which may favor an old bond to reappear (less static hinder).

There are two of them still visible which I found, there may be more but I’m not sure.

The Backwards C (past)

Cloud Lab 6 (current)

I know I have had a few Wisdave where there was a slight drop as temp started rising around 47-57C range. It is fairly rare to see them. I wonder how they would fare in the lab? If I run across any of my past labs with this I will PM you.

A melt temp drop at the left-hand (beginning) side of switch puzzles is quite common. And drops can occur anywhere along the way–think of it as temporary, partial, thermal annealing.