Protein Folding

Question 1

4 what is protein folding?

Answer 1

Proteins consist of polypeptide chains folded into specific, stable configurations
essential for their function (Linus Pauling).

Question 2

4 Primary Structure:

Answer 2

Sequence of amino acids in a single polypeptide chain, using 20 standard L-amino
acids.

Question 3

4 Native conformation

Answer 3

the unique 3D structure of a protein that is functional.

Question 4

4 Levinthal’s Paradox:

Answer 4

Theoretical prediction that proteins would take an astronomically long time to fold if
they sampled all possible conformations.
o Actual folding occurs in milliseconds to seconds, suggesting a more guided process.

Question 5

4 Secondary Structures:

Answer 5

Regular structures like α-helix and β-sheet, which are stabilized by hydrogen bonds
and minimize steric repulsion.
Represented in Ramachandran plots showing allowed Φ, Ψ angles.

Question 6

4 Gibbs Free Energy (ΔGfold):

Answer 6

ΔGfold = ΔHfold - TΔSfold, where:
 ΔHfold: Enthalpy gain from new interactions in folded state.
 -TΔSconf: Entropy loss from reduced degrees of freedom.
 -TΔShydrophobic: Entropy gain from hydrophobic effect.

Question 7

4 Hydrophobic Effect:

Answer 7

Water molecules form an ordered cage around non-polar molecules; breaking this
cage increases system entropy, favoring folding.

Question 8

4 Energy Landscape Models:

Answer 8

Old View: Steep, well-defined energy paths similar to chemical reactions.
New View (Smooth Funnel): High probability of reaching native state due to a
smooth, funneled energy landscape.
Rugged Funnel: Realistic view accounting for multiple pathways and energy barriers,
leading to the native state.

Question 9

4 Principle of Minimal Frustration:

Answer 9

Protein sequences are naturally selected to minimize frustration and optimize folding
into functional structures efficiently.

Question 10

4 Folding Models (intermediate?):

Answer 10

Two-State Model: Proteins fold directly to the native state.
Multi-State Model: Proteins pass through intermediate states.

Question 11

4 Chaperones:

Answer 11

Proteins that assist other proteins in folding correctly and prevent misfolding, crucial
for avoiding diseases like Alzheimer’s.

Question 12

4 SUMMARY OF PROTEIN FOLDING(4)

Answer 12

Driven by non-covalent interactions, creating a low-energy, many-interaction landscape.
Natural sequences are funneled towards the native state, making stabilizing contacts
probable.
Random sequences are unlikely to fold, highlighting the importance of natural selection in
protein evolution.
The native conformation represents the global minimum in the energy landscape, with
proteins being marginally stable.