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.