Nucleic Acid Structure

DNA was first macromolecular structure solved

Part of a protein diffraction pattern

Proteins

• 20 amino acids ($20^{L}$) leads to vast set of possible sequences.
• Have two degrees of backbone freedom ($\Phi$ and $\Psi$).
• 5(ish) pieces of secondary structure ($\alpha$-helix, $\beta$-sheet, $\pi$-helix, loop, turn)
• Folds heirarchically, giving $\approx 1000$ folds

Nucleic acids

• 4 bases ($4^{L}$) leads to slightly less vast set of possible sequences.
• Have 12 degrees of backbone freedom ($\alpha$,$\beta$,$\gamma$,$\delta$,$\varepsilon$,$\eta$,$\chi$,$\nu_{0}$,$\nu_{1}$,$\nu_{2}$,$\nu_{3}$,$\nu_{4}$)
• Bunch of low-order structures: B-form, A-form, Z-form, H-form helices; cruciforms; bubbles, hairpins
• Also folds heirarchically, giving who-knows-how-many folds

Nucleic Acids

Ridiculous numbers of bonds that can rotate

Sugar can "pucker"

Bases form standard "Watson-Crick" hydrogen bonds

But many other hydrogen bond patterns form

Base pairs orient in different ways relative to axis of strand

There are three basic classes of nucleic acid helix: A, B, and Z

What stabilizes a given nucleic acid structure?

• Hydrogen bonds
• Base stacking
• Electrostatics

Hydrogen bonding

G-C: $-10\ kJ\cdot mol^{-1}$

A-T: $-1\ kJ\cdot mol^{-1}$

Base stacking

Electrostatics

• Positive ions offset negative charge on backbone
• Divalent ions (particularly magnesium) often play structural roles

Higher-ordered stuff

• Compact structures
• Super long DNA
• DNA origami

Roadkill diagrams show secondary structure

Stem-loop (a.k.a. hairpin)

G-quadraplex

Flipping between secondary structures allows regulation

Holliday junctions occur in recombination

Secondary structure can assemble into tertiary structure

Secondary structure can assemble into tertiary structure

Ribozymes: catalytically active RNA molecules

Super long DNA: Chromatin

Super long DNA: NETosis

Super long DNA: Supercoiling

Super long DNA: Persistence length

Measures how far you have to go until bending at one spot is not correlated with bending at another

• Cooked spaghetti: a few cm
• Dry spaghetti: $10^{18}\ m$
• DNA: $\approx 150\ bp$ ($~\approx 50 \ nm$)

Gives a rough estimate of how far along DNA two things can interact without binding to each other

DNA is now used as a programmable material