Distribution of residues — Which statement about charged and hydrophobic amino acids in folded proteins is most accurate?

Introduction:
Residue distribution in proteins balances hydrophobic effects, hydrogen bonding, and functional needs. This question asks for the most accurate generalization about where charged and hydrophobic residues are found in folded structures.

Given Data / Assumptions:

• Typical soluble globular proteins in aqueous solution.
• Charged residues include Asp, Glu, Lys, Arg, and often His.
• Hydrophobic residues include Leu, Ile, Val, Phe, and others.

Concept / Approach:
Electrostatic and solvation considerations favor exposure of charged groups to water. However, evolution sometimes buries charged residues where they form salt bridges, bind ligands, tune pKa values, or contribute to catalysis. Hydrophobic residues preferentially occupy the core but are not universally buried because surfaces also require hydrophobic patches for interactions and stability.

Step-by-Step Solution:

Verification / Alternative check:
Statistical analyses of protein structures show significant enrichment of charged residues at solvent accessible surfaces, with a smaller fraction buried as functional exceptions. Tyrosine and other aromatics are amphipathic and frequently located near interfaces rather than exclusively in cores.

Why Other Options Are Wrong:

• Never buried: too absolute; buried charged residues do exist.
• All hydrophobics are buried: many are partly exposed, especially at interaction interfaces.
• Tyrosine only interior: Tyr is amphipathic and often at boundaries.
• Glycine always surface: Gly can occur in cores, especially where tight turns or packing flexibility are needed.

Common Pitfalls:
Treating rules of thumb as strict rules. Protein structure is governed by tendencies with meaningful exceptions that support function and stability.

Final Answer:
Charged amino acids are seldom buried in the interior of a protein.