You are performing site-directed mutagenesis to test predictions about which residues are essential for a protein's function. Which of each pair of amino acid substitutions listed below would you expect to disrupt protein function the most?

Question

A. Val replaced by Ala or Phe
B. Lys replaced by Asp or Arg
C. Gln replaced by Glu or Asn
D. Pro replaced by His or Gly

Answer 1

A. Phe. Three of them are non polar. Phe is larger than others, introduce a greater sterical clash.
B. Asp. Lys and Arg are positively charged. Asp is negatively charged.
C. Glu. Gln and Asn are polar side chains. Glu is negatively charged.
D. His. Pro and Gly are non polar. His is basic.

Answer 2

A. Phe
B. Arg
C. Asn
D. His