Structure of DNA Flashcards
Which of the fundamental forces is most important at biological scales?
-when considering biological molecules, electrostatic force is the most important
F = -Q1Q2/4πεr²
-where
ε = εoεr
Derive the Expression for Intermolecular Forces
-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»_space; central molecular diameter σ
-so σ/L«1 => long range interactions can only disappear for n>3
Lennard-Jones Type Potentials
-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
Lennard-Jones Potential
General Form
V(r) = -A/r^6 + B/r^12
Attractive Forces
-london dispersion and van der Waals forces (time dependent electron density)
Repulsive Forces
-pauli exclusion principle (quantum mechanical effect)
Mie Potential
General Form
V(r) = -A/r^n + B/r^m
Life in a Thermal Bath
-for mammalian life, T=37’C
kbT = 4.278pNnm
-so molecular motors (protein enzymes) must generate >4pn of force to travel 1nm
Equipartition Theorem
-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
X-ray Fibre Diffraction of DNA
- 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
Structure of DNA
- right-handed screw
- base pairs
- -two hydrogen bonds between thymine and adenine
- -three hydrogen bonds between cytosine and guanine
Effect of Hydration on DNA
- the A-form of DNA is double stranded and dehydrated
- the B-form of DNA is double stranded and hydrated
Nucleotide Monomer
-sugar, phosphate and base
Sugar Phosphate Backbone
- staircase structure
- sugar of one nucleotide is bonded to the phosphate on the next nucleotide
Structure of Nucleic Acids
Sugar Ring
-proton donor from OH groups, gives acidic properties
Structure of Nucleic Acids
Phosphate Group
- ionise (-1) in aqueous solution, coordinated by Mg2+
- an electron donor, also giving acidic properties
Structure of Nucleic Acids
Nucleotide Base
- four ‘flavours’: C, G, A, T
- contain basic groups (NH2) which accept protons, involved in base pairing
Categorising Base Pairs
- A and G are purines
- C, T and U are pyrimidines
Bonding Between Base Pairs
- 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
DNA vs. RNA Behaviour
- double stranded DNA is a stiff, worm-like polymer
- proteins are folded coils
- RNA has behaviour between them
Is RNA single or double stranded?
-RNA is single stranded but some times folds around creating base pairing regions
Strand Polarity
- 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’
Flipping Out
- 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
Major / Minor Grooves
- 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
