Introduction
Proteins and nucleic acids only work in the right three-dimensional shape. Thermodynamics of biopolymers explains why that shape forms, why it is stable and how it is lost.
Free energy decides the shape
A biopolymer takes the shape with the lowest free energy under the given conditions. Free energy balances enthalpy (H), which reflects bonds, against entropy (S), which reflects disorder:
The folded state must have a lower free energy than the unfolded state. Folding reduces the chain's own freedom, so its entropy falls. Other forces have to make up for this loss.
Protein folding and denaturation
Anfinsen showed that a protein's sequence holds the information for its native shape. A folded protein is only slightly more stable than the unfolded chain, because many large opposing forces nearly cancel out. This lets proteins stay flexible, but it also makes them easy to damage.
Denaturation is the loss of the native shape without breaking the amino acid chain. Heat, extreme pH, urea and detergents can all cause it. It is often cooperative: once part of the structure opens, the rest quickly follows, so the change happens over a narrow temperature range.