The entropy of heterogeneous random coil or denatured proteins is significantly higher than that of the tertiary structure of its folded native state. In particular, the conformational entropy of the amino acid side chains in a protein is thought to be a major contributor to the energetic stabilization of the denatured state and thus a barrier to protein folding. However, a recent study has shown that side-chain conformational entropy can stabilize native structures among alternative compact structures. The conformational entropy of RNA and proteins can be estimated; for example, empirical methods to estimate the loss of conformational entropy in a particular side chain on incorporation into a folded protein can roughly predict the effects of particular point mutations in a protein. Side-chain conformational entropies can be defined as Boltzmann sampling over all possible rotameric states: