Hydrophobic collapse

Hydrophobic collapse is a proposed process for the production of the 3-D conformation adopted by polypeptides and other molecules in polar solvents.

The theory states that the nascent polypeptide forms initial secondary structure (ɑ-helices and β-strands) creating localized regions of predominantly hydrophobic residues.

The polypeptide interacts with water, thus placing thermodynamic pressures on these regions which then aggregate or "collapse" into a tertiary conformation with a hydrophobic core.

Incidentally, polar residues interact favourably with water, thus the solvent-facing surface of the peptide is usually composed of predominantly hydrophilic regions.

Conversely rigid scaffolds (also called privileged structures) that resist hydrophobic collapse may enhance drug affinity.

[2][3][4] Partial hydrophobic collapse is an experimentally accepted model for the folding kinetics of many globular proteins, such as myoglobin,[5] alpha-lactalbumin,[6] barstar,[7] and staphylococcal nuclease.

[9][10] Globular proteins that are thought to fold by hydrophobic collapse are particularly amenable to complementary computational and experimental study using phi value analysis.

Hydrophobic collapse can be visualized as part of the folding funnel model which leads a protein to its lowest kinetically accessible energy state.

Figure 7. Illustration of the hydrophobic collapse during protein folding. In the compact fold (to the right), the hydrophobic amino acids (shown as black spheres) are in general shielded from the solvent.
The folding funnel theory of protein folding
Top-down view of an alpha-helix showing the precedence of similarly polar residues on the same "face" of the helix running longitudinally.
Stylized cartoon showing the overall polarity of either side of an amphipathic alpha helix. One longitudinal side is nonpolar and interacts with the hydrophobic core of the peptide, while the polar side interacts with the polar solvent.