Protein Folding

Question 1

What is meant by protein folding?

Answer 1

The physical process by which an unfolded polypeptide folds into its three-dimensional structure known as the native state or tertiary structure

Question 2

Explain the peptide bond dipole ?

Answer 2

Peptide bond (double bond character and therefore planar. i.e. no rotation)

Question 3

What is a hydrogen bond ?

Answer 3

The electronegative oxygen of water pulls electrons from the Electropositive hydrogen atoms. This results in a dipole and attracts other such dipoles. This is not a covalent bond.

Question 4

Hydrogen bonding can drive?

Answer 4

Nucleation and cooperativity (the zipper model) and therefore protein folding

Question 5

Explain origin of cooperativity?

Answer 5

• The probability of forming contact C2 is much higher if C1 is formed
• C1 acts as a nucleation site

Question 6

Hydrogen bonds (enthalpy) drive ?

Answer 6

• Protein folding down specific pathways
• Folding is NOT random

1. Initiate folding by nucleation (start point of an entry into a folding pathway)
2. Leads to co-operatively (entry to a defined pathway)
3. Leads to specific folding pathways (not a random process)

Question 7

What does side chain packing and hydrogen bonds lead to ?

Answer 7

Some super-secondary structures

Question 8

There are specific angles that allow helix packing. However, which is not possible ?

Answer 8

i+2n (2n) not possible

Question 9

Explain beta-beta packing ?

Answer 9

• Antiparallel β-sheets are often packed against another β-sheet
• The angle between the sheets is determined by their right-handed twist
• Top strand R groups sit between the 4 bottom strand R-groups

Question 10

What drives protein folding, energy wise ?

Answer 10

ΔG = ΔH - TΔS

• ΔG = Free Energy (negative is favourable- net change in energy)
• Ordered (requires energy to maintain unfavourable)
• Random movement (Energetically favourable)

Question 11

When proteins fold two entropic changes occur ?

Answer 11

1. Hydrophobic surface is buried (favourable)-smaller
2. Side chains become static (unfavourable) - bigger
   - The unfavourable part is much greater than the favourable part

Question 12

Explain entropy of oil in water?

Answer 12

• Water is repelled by hydrophobic molecules. They therefore become more ordered. Entropically unfavourable
• HOWEVER, in this case it is Entropically favourable
• But for a protein the side chains become ordered so the process is unfavourable