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Comment by vedtopkar | Hacker News Reader

This coverage is incredibly disingenuous. It's been known for a long time that base stacking is the dominant force in keeping a double helix together.

Literally the first sentence of the abstract is "Hydrophobic base stacking is a major contributor to DNA double-helix stability."

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Agreed, thanks.

I have vague memories of a college professor who had spent a lot of time working out the exact places water would tend to coordinate on the DNA strand as part of his early prior research. His rant on the role of hydrogen bonding in the molecule was memorable.

The authors state their contribution as, "specific longitudinal unstacking in a hydrophobic environment has to our best knowledge never been reported before."

A little background on one of the authors: Carlos Bustamante (there are two science-famous ones, this one is NOT the one who analyzed Elizabeth Warren's DNA test) is a pioneer in structural analysis of DNA, particularly using optical tweezers to study how DNA (and later proteins) behave. As part of that work he has been interested in how tension or compression or other perturbations propagate through the DNA helix. The longitudinal unstacking is part of that.

Full disclosure: in graduate school I worked in a lab that published a paper that contradicted some of his previous work. It was a different part of the lab so I only know the high level overview of the controversy. He's a giant in the field though.

It may not be disingenuous. Judging by all the repetition in the article it was probably by written by someone who had no idea what the researchers were talking about.

So this sentence is uncontroversial? Somehow I never came across this idea in my genetics PhD.

> The main stabilizer of the DNA double helix is not the base-pair hydrogen bonds but coin-pile stacking of base pairs, whose hydrophobic cohesion, requiring abundant water, indirectly makes the DNA interior dry so that hydrogen bonds can exert full recognition power.

"Often overlooked" might be a better term. This seems to be well-known to biophysicists studying nucleic acids but doesn't trickle down to the genetics/biology side of things.

That statement is uncontroversial, though keep in mind it's also not completely rejecting the importance of H-bonds. A GC basepair is still more stable than an AT basepair due to 3 H-bonds on the GC and only 2 for the AT. However, to compute DNA helix stability you must take into account the stacking of basepairs. Modern melting point calculators have correction terms that take stacking between different pairs of base pairs (AT stacking on a GC, AT stacking on a TA, etc.). They also take into account salt concentration, which is absolutely critical to maintaining helix stability. This is because the salt coordinates with the phosphate backbone, stabilizing the helix.

Key rule of thumb for pretty much any biological structure: it's the entropy not the enthalpy that dominates. Entropy in this context is the stacking of base pairs, enthalpy is formation of electrostatic or similar bonds (like an H-bond between DNA bases). Essentially every biological molecule is "greasier" than water, so it likes to hide that "grease" from the water much the same way oil likes to form droplets with itself in water because doing so reduces the "order" and therefore the boosts the total entropy of the solution.

Why you ask? It's complicated but my general understanding is that water that is interacting with "grease" has to adopt a fair amount of structure. By reducing the number of water molecules contacting your "grease" you reduce the amount of structure the water has, which means the total system is more disordered even as the grease itself adopts a higher degree of structure.

This is all a little handwavy, it's been a while since thermo, but it's a decent overall framework for general understanding.

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