Protein disorder upon unfolding: What is the effect on entropy when regular secondary structure (α-helix/β-sheet) unfolds into a random coil?

Introduction / Context:
Entropy (disorder) plays a central role in protein stability. While folding can be enthalpically favorable due to noncovalent interactions, the unfolded chain has many more accessible conformations, dramatically affecting the entropy term in the free energy balance.

Given Data / Assumptions:

• Regular secondary structures constrain backbone dihedral angles (ϕ, ψ) to narrow regions.
• Unfolding releases these constraints, increasing conformational freedom.
• We consider the protein’s conformational entropy specifically.

Concept / Approach:
Entropy S reflects the number of accessible microstates. An ordered helix/sheet permits far fewer microstates than a flexible random coil. Thus, unfolding increases protein conformational entropy substantially, although solvent entropy can counterbalance during hydrophobic collapse in folding.

Step-by-Step Solution:
Helix/sheet → restricted ϕ/ψ angles, low conformational variance. Unfolding → many backbone and side-chain rotamers become accessible. Microstate count rises sharply → entropy increases. Therefore, unfolding produces a large increase in protein entropy.

Verification / Alternative check:
Statistical thermodynamics and calorimetry support that conformational entropy is a major opposing term to folding; heat-denaturation increases configurational freedom.

Why Other Options Are Wrong:
Decrease/no change contradicts the definition of conformational entropy; “little increase” underestimates the substantial rise.

Common Pitfalls:
Ignoring solvent entropy (hydrophobic effect) and overgeneralizing—here the question focuses on the protein’s entropy.

Final Answer:
Large increase in the entropy of the protein.