Final answer:
Hydrophobic side chains cluster in the interior of a folded polypeptide, away from water, forming the protein's tertiary structure.
Step-by-step explanation:
The hydrophobic side chains tend to cluster at the interior of a folded polypeptide, away from the aqueous surroundings.
In the folded structure of a protein, also known as its tertiary structure, hydrophobic and non-polar side chains spontaneously come together in the interior to avoid water. This is aided by the formation of various non-covalent bonds like hydrogen bonds and salt bridges. On the surface of the molecule, hydrophilic side chains are found where they can interact with the external aqueous environment.
These interactions, including hydrophobic interactions and the formation of disulfide bridges between cysteine side chains, determine the protein's final three-dimensional shape, which is crucial for its function.