This is a real-world medical entrance exam question, please give the true answer based on the question and selection. Topic name: None, Subject name: Biochemistry
A mutation is MOST likely to alter the three-dimensional conformation of a protein if: 
Select and explain. 
A. There is a substitution of a hydrophobic amino acid for a hydrophilic amino acid, B. Valine is substituted for leucine, C. It changes the amino acid at the amino-terminus, D. It places proline in the middle of a a-helix
D: It places proline in the middle of a a-helix
Answer: D: It places proline in the middle of a a-helix 
Explanation: The geometry of proline is incompatible with the a-helix. The substitution of a hydrophobic for a hydrophilic amino acid may or may not produce a change in the structure of a protein molecule. Substitution of the hydrophobic valine for another hydrophobic residue, leucine, would be predicted to have little effect on the structure of the protein. Substitution at the amino or carboxyl end of the molecule may or may not produce a change in the protein structure.