Why do nonpolar amino acid side chains tend to be buried inside globular proteins?

Nonpolar amino acid side chains are hydrophobic, meaning they are "water-fearing". In aqueous environments, globular proteins fold into specific three-dimensional shapes to sequester these hydrophobic side chains within the protein's interior.12

This structural arrangement occurs because the folding process is so tight that it displaces most water from the center of the globular molecule. By burying these nonpolar groups, the protein effectively shields them from the surrounding aqueous medium, while amino acids containing charged groups—such as ammonium and carboxyl groups—are shifted to the surface of the molecule where they can interact with water. This organization is essential for the stability and proper conformation of the protein.21