protein folding

Meaning: A polypeptide folds into its native conformation, and its primary sequence largely determines that shape. Anfinsen showed this: ribonuclease denatured with urea and a reducing agent regained activity when both were removed. Hydrophobic side chains cluster in the interior and polar ones face water. Backbone hydrogen bonds form α helices and β sheets (secondary structure). R-group interactions (hydrogen bonds, ionic bonds, van der Waals forces, disulfide bonds) set tertiary structure. Chaperones help some proteins fold by preventing aggregation.

Equation: ΔG = ΔH − TΔS, where ΔG is the free energy change (J/mol), ΔH the enthalpy change (J/mol), T the absolute temperature (K), and ΔS the entropy change (J/(mol·K)). Folding is spontaneous when ΔG < 0.

On the MCAT: Passages describe denaturation by heat, extreme pH, urea, detergents, or reducing agents, and ask whether activity is lost or regained. You may predict the effect of a mutation, such as a buried hydrophobic residue replaced by a charged one (usually destabilizing), or the loss of disulfide bonds.

Common confusion: Denaturation does not break peptide bonds, so primary structure stays intact, which is why some proteins can refold. Also, the chain itself loses entropy when it folds. The favorable entropy gain comes from water freed from around hydrophobic groups (the hydrophobic effect).