Question

When a protein folds, which is the driving force for folding of a protein – enthalpy or entropy? Explain briefly your reasoning

Answer 1

The folding of a protein also provides an example of the "?H" and "–T?S" terms competing with one another to determine the ?G of the folding process. As described above, the change in entropy of the protein as it folds is negative, so the "–T?S" term is positive. However, in addition to entropic effects there are enthalpic contributions to protein folding. These include hydrogen bonding, ionic salt bridges, and Van der Waals forces. An input of thermal (heat) energy is required to disrupt these forces, and conversely when these interactions form during protein folding they release heat (the ?H is negative). When all of these entropic and enthalpic contributions are weighed, the enthalpy term wins out over the entropy term. Therefore the free energy of protein folding is negative, and protein folding is a spontaneous process.