Passage
The primary structure of a protein is a series of amino acids that are connected in a long chain via C−N peptide bonds (Figure 1) .
Figure 1 Peptide bonds within a protein segment (Note: Rⁿ = amino acid side chains) Protein chain folding is guided by multiple intramolecular interactions that can occur between two peptide bonds, between a peptide bond and a side chain, or between two side chains, as shown in the protein in Figure 2. Although these interactions are intramolecular because they are within the same molecule, they act effectively like intermolecular interactions because proteins are such large molecules.
Figure 2 Intramolecular interactions between the peptide chain and amino acid side chains within a hypothetical proteinBecause intramolecular interactions play a significant role in maintaining the three-dimensional folded structure of a protein, having a greater number of interactions or stronger interactions will result in increased protein stability. The energy required to break these interactions within a protein is related to free energy, ΔG. The greater the ΔG value, the more stable the protein.To find the overall contribution of particular intramolecular interactions to protein stability, researchers made several protein variants in which one amino acid is replaced by another to change the noncovalent interactions between the side chains. The difference in free energy between the variant and the original protein, Δ(ΔG) , indicates the change in overall stability of the protein. A negative Δ(ΔG) means the variant protein is less stable than the original.Table 1 shows the results of the amino acid substitution experiments for a protein with the approximate energy difference when each amino acid is changed.Table 1 Change in Free Energy Based on Changing Intramolecular Interactions Caused by Amino Acid Substitutions
Adapted from: C. N. Pace, J. M. Scholtz, G. R. Grimsley, "Forces stabilizing proteins." FEBS Lett. ©2014 Wiley.
-Assuming the amino acid substitutions found in Table 1 occur on the protein surface, which substitution would cause the smallest change in the water solubility of the protein?

Question

Passage
The primary structure of a protein is a series of amino acids that are connected in a long chain via C−N peptide bonds (Figure 1) .

Figure 1 Peptide bonds within a protein segment (Note: Rⁿ = amino acid side chains) Protein chain folding is guided by multiple intramolecular interactions that can occur between two peptide bonds, between a peptide bond and a side chain, or between two side chains, as shown in the protein in Figure 2. Although these interactions are intramolecular because they are within the same molecule, they act effectively like intermolecular interactions because proteins are such large molecules.

Figure 2 Intramolecular interactions between the peptide chain and amino acid side chains within a hypothetical proteinBecause intramolecular interactions play a significant role in maintaining the three-dimensional folded structure of a protein, having a greater number of interactions or stronger interactions will result in increased protein stability. The energy required to break these interactions within a protein is related to free energy, ΔG. The greater the ΔG value, the more stable the protein.To find the overall contribution of particular intramolecular interactions to protein stability, researchers made several protein variants in which one amino acid is replaced by another to change the noncovalent interactions between the side chains. The difference in free energy between the variant and the original protein, Δ(ΔG) , indicates the change in overall stability of the protein. A negative Δ(ΔG) means the variant protein is less stable than the original.Table 1 shows the results of the amino acid substitution experiments for a protein with the approximate energy difference when each amino acid is changed.Table 1 Change in Free Energy Based on Changing Intramolecular Interactions Caused by Amino Acid Substitutions

Adapted from: C. N. Pace, J. M. Scholtz, G. R. Grimsley, "Forces stabilizing proteins." FEBS Lett. ©2014 Wiley.
-Assuming the amino acid substitutions found in Table 1 occur on the protein surface, which substitution would cause the smallest change in the water solubility of the protein?

Quizplus · Accepted Answer

11ecba2d_11ef_8ffc_a3bf_13d06010b1eb_MD0008_00 For a compound to be soluble in water, there must be enough intermolecular interactions between the structure of the compound and the structure of the water molecules to enable the compound molecules to be solvated (individually surrounded by) water molecules and carried into solution. Because the O−H bonds in water are highly polar with a strong dipole moment, a compound will dissolve in water only if its structure has a sufficient number of polar sites for intermolecular interactions with the polar water molecules. A hydrophobic ("water-fearing") molecule is sparingly soluble in water because it is predominantly nonpolar and lacks enough polar sites for dipole interactions with water. Conversely, hydrophilic ("water-loving") molecules have a sufficient number of polar sites to be soluble in water. For a protein to be soluble in water, its surface must have enough polar interactions with the polar water molecules. Structural changes that increase polar sites on the protein surface will enhance water solubility, but changes that decrease polar sites will decrease water solubility. However, replacing one polar (or nonpolar) site with something that has similar characteristics will cause little or no change in solubility. Isoleucine and valine both have nonpolar side chains of similar size. Consequently, replacing isoleucine with valine would not significantly change the solvent interactions with the protein surface, and would cause little (if any) change in the water solubility of the protein. (Choice A, B, and C) Serine, threonine, and tyrosine all have side chains with an -OH group capable of hydrogen bonding. Replacing serine with alanine, threonine with valine, or tyrosine with phenylalanine would remove an -OH group, leaving a nonpolar side chain. This would decrease the number of polar sites on the protein surface and substantially decrease the protein solubility. Educational objective: Water solubility requires that a compound has enough polar intermolecular interactions between the structure of a compound and the water molecules that the compound can be solvated and carried into solution. Hydrophobic molecules tend to be predominantly nonpolar and are sparingly soluble in water. Structural changes that increase polar sites on a molecule will enhance water solubility.

Passage the Primary Structure of a Protein Is a Series of of Amino