[et2o]

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.

[entee]

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.

[caillancm]

"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.