9.5. Thermal, chemical, and mechanical switching[[Student version, January 17, 2003]] 327
the disordered state at high, not low, temperature. That is, DNA undergoes a sharp transition
as its temperature is raised past a definite melting point. Because of the general similarity to the
alpha-helix transition in polypeptides, many authors refer to DNA melting as another “helix–coil”
transition.
Tounderstand DNA melting qualitatively, we visualize each backbone of the duplex as a chain
of sugar and phosphate groups, with the individual bases hanging off this chain like the charms on
abracelet. When the duplex melts, there are several contributions to the free energy change:
1.The hydrogen bonds between paired bases break.
2.The flat bases on each strand stop being neatly stacked like coins; that is, theyunstack.
Unstacking breaks some other energetically favorable interactions between neighboring bases,
like dipole–dipole and van der Waals attractions.
3.The indvidual DNA strands are more flexible than the duplex, leading to an increase in the
backbone’s conformational entropy. The unstacked bases can also flop about on the backbone,
giving another favorable entropic contribution to the free energy change.
4.Finally, unstacking exposes the hydrophobic surfaces of the bases to the surrounding water.Under typical conditions,
- DNA melting is energetically unfavorable (∆E>0). This fact mainly reflects items #1 and
#2 above. But, - Unstacking is entropically favored (∆S>0). This fact reflects the dominance of item #3
overthe entropic part of item #4.
Thus, raising the temperature indeed promotes melting: ∆E−T∆Sbecomes negative at high
temperature.
Now consider the reverse process, the “reannealing” of single-stranded DNA. The above logic
suggests that there will be a large entropic penalty to bring two flexible single strands of DNA
together, initiating a duplex tract. Thus we expect to find cooperativity, analogously to the situation
in Section 9.5.2. In addition, the unstacking energy is an interaction between neighboring basepairs,
and so encourages the extension of an existing duplex tract more than the creation of a new one.
The cooperativity turns out to be significant, leading to the observed sharp transition.
9.5.5 Applied mechanical force can induce cooperative structural tran-
sitions in macromolecules
Sections 9.2–9.4 showed how applying mechanical force can change the conformation of a macro-
molecule in the simplest way, by straightening it. Sections 9.5.1–9.5.4 discussed another case,
with a more interesting structural rearrangement. These two themes can be combined to study
force-induced structural transitions:
Whenever a macromolecule has two conformations which differ in the distance
between two points, then a mechanical force applied between those points will
alter the equilibrium between the two conformations,(9.27)
Idea 9.27 underlies the phenomenon ofmechanochemical coupling.Wesawthis coupling in a
simple context in our analysis of molecular stretching, via the external part of the energy function,