Switch question from Edward Lane
I’m passing on a question about the estimate mode in switch lab on from Edward Lane. I tried answer the part I could. Please feel free to add what you know about this. your take on this.
Here is the original question:
“In the estimate mode the red glow that marks where the aptamer site ought to be is in two places - that do not form the opposite sides of a loop, if I recall correctly they are shown as being part of a stack and part of an unconnected loop.”
Or as he reformulated it:
“If the red glow doesn’t (in the estimate mode) make the same/similar shape it did in the target mode, does that mean that the aptamer molecule is not actually ‘bound’ - so ‘switching’ failed ?” or phrased differently - what does the location of the red glow ‘mean’ in terms of binding/free energy/etc.
(chatlog outline with added pictures)
Edward_Lane: can someone confirm that the estimate mode in switch labs only ‘works’ properly for the unswitched state ?
Eli Fisker: Ed do you mean in general?
Edward_Lane: @eli I meant in general, looking at the link you gave now
Eli Fisker: Ok, but lately we did get acces to get the binding state fold in switches too
Eli Fisker: Earlier we couldn’t do in switches
Eli Fisker: I mean I can make the estimate fold in binding shape too
Edward_Lane: @eli yes I can make it but it doesn’t make ‘sense’
Edward_Lane: @ eli look at
Edward_Lane: brourd swich test 1
Edward_Lane: and then brourd’s submission - which was at the top
Edward_Lane: @eli, first I look at the target shapes for bound/unbound, and I see that bases 20 to 27 ‘hold’ the molecule
Edward_Lane: then I go to the unbound state (1) and the flask to show estimated result
Edward_Lane: then staying on the flask but switching to 2 (the bound state) I see a tiny change in the shape - unpairing bases 27 and 43 (with very little change in the blue/white/yellow info
Eli Fisker: No binding molecule in the second state according to the estimate
Edward_Lane: but the bit that doesn’t make sense to me is that the ‘red glowing stuff’ which supposedly marks where the aptamer should live doesn’t exist
Eli Fisker: ah
Eli Fisker: I can’t explain that.
Jieux: I like red glowing stuff.
Eli Fisker: The estimate itself makes sense in the way that it does resembles the shape 1 most
Edward_Lane: yes exactly, seem the same for other puzzles it seems that the ‘shape data’ passed to the ‘estimate’ mode doesn’t include anything to ‘constrain/boost’ the aptamer binding site as being otherwise ‘unbound’
Eli Fisker: and state 1 receive highest score.
Later explanation: I think the reds and the white ring marked nucleotides in the estimate mode function is to point out where the aptamer should have been positioned if the switch has went well. So I don’t think it is the estimate mode that is not working, but that it in this case is the switch that is not working.
I then switch to the estimate. And the red markings occur in exact the area between 20-27 and 51-57