A short segment of a polypeptide chain in aqueous solution has the sequence
Ser–Lys–Val–Asn–Asp
The side-chain characteristics are given below.
• Ser (–CH2OH): polar, capable of hydrogen bonding
• Lys (–(CH2)4NH3+): positively charged at physiological pH
• Val (–CH(CH3)2): nonpolar, hydrocarbon
• Asn (–CH2CONH2): polar, capable of hydrogen bonding
• Asp (–CH2COO−): negatively charged at physiological pH
(1) When the polypeptide folds, identify all significant non-covalent interactions that could form (i) between different side chains within the segment and (ii) between side chains and surrounding water molecules.
(2) Predict how replacing Val with Phe (–CH2C6H5) would influence the overall stabilization energy arising from dispersion forces in the folded protein. Explain your reasoning with reference to molecular size and polarizability.
(3) Lys and Asp residues are often found in close proximity in folded proteins. Using your analysis from part (a), justify how this proximity can contribute to the stability of the tertiary structure under physiological conditions.