Protein Folding

Question 1

What is the principle of protein folding?

Answer 1

The interior of protein is hydrophobic and the exterior is hydrophilic.
- it is driven by shielding of hydrophobic group from solvent.
Membrane protein are ‘inside out’ as they exist in the hydrophobic medium of the membrane.

Question 2

How does protein folds?

Answer 2

Amino Acid have a preference for different secondary structural conformations

Question 3

What is Levinthal’s paradox?

Answer 3

• This proves that protein folding is not random, must have pathways.
• Protein folding can’t be a random selection of all possibilities
• The key is the idea of progressive stabilisation of intermediates.
• Cumulative selection of partially correct folding states leads to a much more rapid search to the lowest energy state- the folded protein.

Question 4

What is co-operative behaviour?

Answer 4

• it is between partially correct folded states rapidly promotes correct folding.
• Local areas of sequence with structural preferences interact with each other, leading to global folding at the lowest energy state.

Question 5

What is molten globule?

Answer 5

Molten globule an intermediate conformational state between the native and the fully unfolded states of a globular protein

Question 6

How molten globule forms?

Answer 6

The formation is driven by the hydrophobic side chain burial. Subsequent ‘fine-tuning’ of a fold to find stable, unique confirmation is slow.

Question 7

What is BPTI?

Answer 7

Bovine pancreatic trypsin inhibitor, it has many possible unfolded state to a single folded state. It is a small, simple but stable protein.
Three disulphides bond, disulphide bond isomerases rearrange them.

Question 8

What is free energy?

Answer 8

The energy in a physical system that can be converted to do work.
The free energy must be negative for a reaction to occur spontaneously.

Question 9

What is Gibbs free energy?

Answer 9

The energy that can be converted into work at a uniform temperature and pressure.

Question 10

What is the second law of dynamics?

Answer 10

The total entropy of a system increases over time, The universe is constantly becoming more disordered.

Question 11

What is enthalpy?

Answer 11

• Enthalpy is the measure of the heat released during a reaction.
• Reaction that gives off heat and results in lower internal energy are favoured.
  “things are lazy”

Question 12

What is entropy?

Answer 12

• the measure of disorder

“ things want to be free”

Question 13

Entropic cooling of mixing a Martini

Answer 13

ice in water 0ºc
Ice in alcohol -4ºc
The entropy of the water/alcohol mixture is greater than just water. “The mixture is more disordered.”