To minimize disruption to a protein’s three-dimensional structure when substituting an amino acid, you typically look for amino acids with similar properties. In this case, you have isoleucine (I) at position 54, which is an aliphatic, nonpolar amino acid. Amino acids with similar properties to isoleucine in terms of aliphatic and nonpolar characteristics include leucine (L) and valine (V).
So, substituting isoleucine at position 54 with leucine or valine would be expected to cause the least disruption in the protein’s three-dimensional structure because they share similar properties. These substitutions involve changing one aliphatic, nonpolar amino acid with another, which is less likely to significantly affect the protein’s overall structure and function.