A mutation is MOST likely to alter the three-dimensional conformation of a protein if:
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.
There is a substitution of a hydrophobic amino acid for a hydrophilic amino acid
Valine is substituted for leucine
It changes the amino acid at the amino-terminus
It places proline in the middle of a a-helix