Structure of DNA

Question 1

Which of the fundamental forces is most important at biological scales?

Answer 1

-when considering biological molecules, electrostatic force is the most important
F = -Q1Q2/4πεr²
-where
ε = εoεr

Question 2

Derive the Expression for Intermolecular Forces

Answer 2

-intermolecular forces need to have more rapid decay lengths than just an electrostatic force
-guess a general attractive interactive potential:
V(r) = -Cm1m2/r^n
=>
F(r) = -dV/dr = -nCm1m2/r^(n+1)
-for discrete molecular masses m1 and m2
-change from discrete masses to a continuum with density ρ
-the continuum shell radius L&raquo_space; central molecular diameter σ
-so σ/L«1 => long range interactions can only disappear for n>3

Question 3

Lennard-Jones Type Potentials

Answer 3

-the equilibrium position of two molecules is at the minimum of the W(r) curve which is at the equilibrium separation
F(r) = -dW/dr
-negative energy means an attractive force, positive energy means a repulsive force
-Fmax at the minimum of the F(r) curve

Question 4

Lennard-Jones Potential

General Form

Answer 4

V(r) = -A/r^6 + B/r^12

Question 5

Attractive Forces

Answer 5

-london dispersion and van der Waals forces (time dependent electron density)

Question 6

Repulsive Forces

Answer 6

-pauli exclusion principle (quantum mechanical effect)

Question 7

Mie Potential

General Form

Answer 7

V(r) = -A/r^n + B/r^m

Question 8

Life in a Thermal Bath

Answer 8

-for mammalian life, T=37’C
kbT = 4.278pNnm
-so molecular motors (protein enzymes) must generate >4pn of force to travel 1nm

Question 9

Equipartition Theorem

Answer 9

-each mode of translation/vibration has kbT/2 of energy
-in 1D systems
–for a fluid:
1/2 m v² = 1/2 kb T
–for a solid:
1/2 k = 1/2 kb T

Question 10

X-ray Fibre Diffraction of DNA

Answer 10

• DNA extracted from cellular material by alcohol precipitation and aligned into a fibre containing millions of aligned DNA molecules
• vertical repeats (n=1,2,3,etc.) in the x-ray image is the separation of the base pairs
• characteristic X shape of image due to the helicity of the molecule

Question 11

Structure of DNA

Answer 11

• right-handed screw
• base pairs
• -two hydrogen bonds between thymine and adenine
• -three hydrogen bonds between cytosine and guanine

Question 12

Effect of Hydration on DNA

Answer 12

• the A-form of DNA is double stranded and dehydrated

- the B-form of DNA is double stranded and hydrated

Question 13

Nucleotide Monomer

Answer 13

-sugar, phosphate and base

Question 14

Sugar Phosphate Backbone

Answer 14

• staircase structure

- sugar of one nucleotide is bonded to the phosphate on the next nucleotide

Question 15

Structure of Nucleic Acids

Sugar Ring

Answer 15

-proton donor from OH groups, gives acidic properties

Question 16

Structure of Nucleic Acids

Phosphate Group

Answer 16

• ionise (-1) in aqueous solution, coordinated by Mg2+

- an electron donor, also giving acidic properties

Question 17

Structure of Nucleic Acids

Nucleotide Base

Answer 17

• four ‘flavours’: C, G, A, T

- contain basic groups (NH2) which accept protons, involved in base pairing

Question 18

Categorising Base Pairs

Answer 18

• A and G are purines

- C, T and U are pyrimidines

Question 19

Bonding Between Base Pairs

Answer 19

• two hydrogen bonds between T and A
• three hydrogen bonds between C and G
• there is an energetic difference between double helix stability for A T rich vs C G rich regions

Question 20

DNA vs. RNA Behaviour

Answer 20

• double stranded DNA is a stiff, worm-like polymer
• proteins are folded coils
• RNA has behaviour between them

Question 21

Is RNA single or double stranded?

Answer 21

-RNA is single stranded but some times folds around creating base pairing regions

Question 22

Strand Polarity

Answer 22

• RNA and DNA are polymerised through covalent bonds between phosphate groups and either 3’ or 5’ carbon on the sugar ribose ring so one strand of nucleic acid has a polarity
• 3’-5’ or 5’-3’

Question 23

Flipping Out

Answer 23

• due to the single line of bonds in the sugar-phosphate backbone nucleotide bass can be rotated around the backbone axis i.e. flipping out
• this is important for enzymes that work on DNA which control epigenetic patterning

Question 24

Major / Minor Grooves

Answer 24

• DNA is like a twisted ribbon
• enzymes recognise major/minor grooves to perform maintenance and copy DNA
• small drug molecules can preferentially bind to grooves to disrupt biological functions

Question 25

Polymorphs of Double Stranded DNA

Answer 25

• the level of hydration and axial tension on the molecule determines helical configuration
• size of the major and minor grooves changes with helical pitch

Question 26

Z-DNA

Answer 26

• DNA where bases have flipped out

- becomes left hand screwed

Question 27

B-DNA

Answer 27

• the hydrated for of DNA
• right handed screw
• helical repeat is 3.4nm or 10.5 base pairs