12. Which one of the statements on protein conformation, detailed below is INCORRECT?
    (1) L- amino acids can occur in Type l’ ß- turns where ϕ, Ψ are positive
    (2) A peptide rich in proline is unlikely to adopt α- helical structure
    (3) Proline residues have high propensity to occur in ß- turns
    (4) The dihedral angles ϕ, Ψ of amino acids in unfolded proteins are exclusively positive

Protein Conformation: Understanding Dihedral Angles and Secondary Structures

Proteins adopt specific conformations determined by their backbone dihedral angles (ϕ and Ψ). These angles define various secondary structures such as α-helices, β-turns, and unfolded states. However, some commonly believed facts about protein conformation are incorrect.

Correct Answer:

The incorrect statement is:

(4) The dihedral angles ϕ, Ψ of amino acids in unfolded proteins are exclusively positive.

Explanation of the Answer Choices

1. L-Amino Acids in Type I’ β-Turns (Correct Statement)

• β-turns allow proteins to form compact structures.
• Type I’ β-turns occur in left-handed configurations, where ϕ and Ψ angles are positive.
• Glycine and asparagine are often found in β-turns due to their flexibility.

2. Proline Prevents α-Helical Structures (Correct Statement)

• Proline disrupts α-helices because:
  • Its rigid pyrrolidine ring restricts ϕ angle rotation.
  • It lacks an amide hydrogen, preventing intra-helical hydrogen bonding.
• Thus, proline-rich peptides do not form stable α-helices.

3. Proline in β-Turns (Correct Statement)

• Proline is commonly found in β-turns due to its ability to introduce kinks in the polypeptide chain.
• Cis-proline is frequently observed in turn structures.

4. Dihedral Angles in Unfolded Proteins Are Not Exclusively Positive (Incorrect Statement)

• Unfolded proteins lack a defined structure, meaning their ϕ and Ψ angles are randomly distributed.
• Both positive and negative dihedral angles are observed in disordered regions.
• Intrinsic disorder in proteins allows for a wide range of φ and Ψ values.

Significance of Understanding Protein Conformation

1. Protein Folding and Stability

• Secondary structures determine the stability and function of proteins.
• Incorrect dihedral angles lead to protein misfolding disorders.

2. Role in Structural Bioinformatics

• Ramachandran plots help validate protein structures in computational modeling.

3. Application in Drug Design

• Understanding protein flexibility aids in designing therapeutic inhibitors.

Conclusion

While β-turns, α-helices, and proline’s role in structure formation are well understood, the claim that unfolded proteins have exclusively positive ϕ and Ψ values is incorrect. Proteins in unfolded states exhibit a diverse range of dihedral angles, reflecting their dynamic nature.