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Confusing AAMC Question regarding DNA
Korolos_5348
#1 Posted : Friday, July 03, 2020 9:28:27 PM
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Hello,

I was completing some of the AAMC practice problems and I came across a question that I do not understand. The question stem is "What causes duplex DNA with a certain (A + T):(G + C) ratio to melt at a higher temperature than comparable length duplex DNA with a greater (A + T):(G + C) ratio?"

The possible answers are listed below

A.Stronger van der Waals forces of pyrimidines
B.Stronger van der Waals forces of purines
C.Increased π- stacking strength
D.Reduced electrostatic repulsion of phosphates

I initially thought that the answer would be related to a higher G/C content having more Hydrogen bonding however that wasn't an answer choice. The correct answer is C. Would someone be able to explain this to me as I have never heard of "Pi stacking" and what its relation is to Hydrogen bonding?

Thank you in advance
INSTR_Katerina_102
#2 Posted : Saturday, July 04, 2020 2:26:19 AM
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Hello,

Thanks for posting the full set of answers.

I would have also have expected H bonding to be mentioned as it is the canonical explanation for melting temperature.

However, because it is not mentioned here, we look at the answers given and eliminate as follows:

Phosphate electrostatics isn't affected by the type of base pairing, so we can likely eliminate D.

Both base pairs A T and C G contain 1 pyrimidine and 1 purine, so A and B don't make sense given that the question states (A + T):(G + C) ratio changes melting temperature.

From there you can guess C, even without knowing what pi stacking is, as the other answers aren't good based on your basic knowledge.

This seems to be an silly strategy to be advocating, but it is good to practice because it is highly likely that on test day the MCAT will invoke at least some concepts you do not know (at least it did for me) - and knowing how to deduce from what you do know really helps deal with this type of question.

However, I understand that this elimination process may not be satisfying, so I'll just briefly describe pi stacking here.

Say you have 2 base pairs AT and CG in a sequence 5'AC3' (I have ommited one strand here).

A and T interact with each other through H bonding, and C and G also through H bonding. However, the bases A and C interact through pi stacking, and T and G also interact through pi stacking.

This way, sequential base pairs which are flat and aromatic will "stack" on top of each other like a bunch of plates - which is really interesting, because it means strand melt temperature is not only a function of how many CG pairs you have, but what base pairs you have beside each other.

Pi stacking can occur between and stabilize all types of aromatic molecules, but the most biologically relevant molecule is DNA due to its flat aromatic base pairs.

For further reference, this is a paper based on the topic they are referring to in this question. Look at the picture under the abstract as this illustrates the pi stacking between two base pairs.

https://pubs.rsc.org/en/...ing/2014/cp/c4cp00997e#!divAbstract

Please let me know if this is unclear, especially the picture in the article.
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