Which one of the following is unfavorable for protein folding?
(1) Hydrophobic interaction
(2) van der Waals interaction
(3) Conformational entropy
(4) Hydrogen bonding

Factors Affecting Protein Folding: Favorable and Unfavorable Interactions

Protein folding is a crucial biological process driven by various intermolecular and intramolecular forces. Some interactions favor folding, while others act as opposing forces. Understanding these factors is essential for biochemistry and structural biology.

Correct Answer:

The correct option is (3) Conformational entropy.

Explanation:

Favorable Factors for Protein Folding:

(1) Hydrophobic Interaction ✅ (Favorable)

• Hydrophobic interactions drive the collapse of non-polar amino acids into the protein core.
• This reduces water entropy and increases overall system stability.
• Plays a major role in stabilizing tertiary and quaternary structures.

(2) van der Waals Interaction ✅ (Favorable)

• Weak but essential non-covalent interactions.
• Induced dipoles in closely packed atoms help stabilize secondary and tertiary structures.
• Important in protein-ligand and protein-protein interactions.

(4) Hydrogen Bonding ✅ (Favorable)

• Hydrogen bonds stabilize secondary structures like α-helices and β-sheets.
• Also contribute to specificity in protein folding.

Unfavorable Factor for Protein Folding:

(3) Conformational Entropy ❌ (Unfavorable)

• Entropy refers to the disorder of a system.
• Unfolded proteins have many possible conformations (high entropy).
• During folding, the polypeptide adopts a specific structure, reducing entropy.
• This loss of conformational entropy is unfavorable, opposing the folding process.

Thus, the correct answer is (3) Conformational entropy, as it resists protein folding.

Nearby Topics for Better Understanding

1. Thermodynamics of Protein Folding

• ΔG (Gibbs free energy) = ΔH – TΔS
  • ΔH (Enthalpy): Favorable due to hydrogen bonds and van der Waals forces.
  • TΔS (Entropy change): Unfavorable due to reduction in conformational entropy.
• Protein folding occurs when ΔG is negative (favorable).

2. Role of Molecular Chaperones

• Prevent misfolding by assisting proteins to reach the correct conformation.
• Examples: Hsp70, GroEL/GroES (chaperonins).

3. Diseases Related to Protein Misfolding

• Alzheimer’s disease (Amyloid-β aggregation)
• Parkinson’s disease (α-synuclein aggregation)
• Prion diseases (Misfolded prion proteins)

Conclusion

While hydrophobic interactions, van der Waals forces, and hydrogen bonds favor protein folding, conformational entropy opposes it by resisting the transition from an unfolded to a folded state. Understanding these factors is essential for predicting protein stability and function.