chemical thermodynamics Chemical thermodynamics is the study of the interrelation of heat and work with chemical reactions or with physical changes of state within the confines of the laws of thermodynamics. Chemical thermodynamics involves not only laboratory measure ...

, conformational entropy is the

entropy Entropy is a scientific concept, most commonly associated with states of disorder, randomness, or uncertainty. The term and the concept are used in diverse fields, from classical thermodynamics, where it was first recognized, to the micros ...

associated with the number of conformations of a

molecule A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

. The concept is most commonly applied to biological

macromolecule A macromolecule is a "molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass." Polymers are physi ...

s such as

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s and

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

, but also be used for

polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long-chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with wat ...

s and other molecules. To calculate the conformational entropy, the possible conformations of the molecule may first be discretized into a finite number of states, usually characterized by unique combinations of certain structural parameters, each of which has been assigned an

energy Energy () is the physical quantity, quantitative physical property, property that is transferred to a physical body, body or to a physical system, recognizable in the performance of Work (thermodynamics), work and in the form of heat and l ...

. In proteins, backbone dihedral angles and side chain rotamers are commonly used as parameters, and in RNA the

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...

ing pattern may be used. These characteristics are used to define the

degrees of freedom In many scientific fields, the degrees of freedom of a system is the number of parameters of the system that may vary independently. For example, a point in the plane has two degrees of freedom for translation: its two coordinates; a non-infinite ...

(in the

statistical mechanics In physics, statistical mechanics is a mathematical framework that applies statistical methods and probability theory to large assemblies of microscopic entities. Sometimes called statistical physics or statistical thermodynamics, its applicati ...

sense of a possible "microstate"). The conformational entropy associated with a particular structure or state, such as an alpha-helix, a folded or an unfolded protein structure, is then dependent on the probability of the occupancy of that structure. The entropy of heterogeneous random coil or denatured proteins is significantly higher than that of the

tertiary structure Protein tertiary structure is the three-dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains and the ...

of its folded native state. In particular, the conformational entropy of the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

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 Protein folding is the physical process by which a protein, after Protein biosynthesis, synthesis by a ribosome as a linear chain of Amino acid, amino acids, changes from an unstable random coil into a more ordered protein tertiary structure, t ...

.Doig AJ, Sternberg MJE. (1995). Side-chain conformational entropy in protein folding. ''Protein Science'' 4:2247-51. However, a recent study has shown that side-chain conformational entropy can stabilize native structures among alternative compact structures.Zhang J, Liu JS (2006) On Side-Chain Conformational Entropy of Proteins. PLoS Comput Biol 2(12): e168. 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:Pickett SD, Sternberg MJ. (1993). Empirical scale of side-chain conformational entropy in protein folding. ''J Mol Biol'' 231(3):825-39. :

S = -R \sum_ p_ \ln p_

where is the gas constant and is the probability of a residue being in rotamer . The limited conformational range of proline residues lowers the conformational entropy of the denatured state and thus stabilizes the native states. A correlation has been observed between the thermostability of a protein and its proline residue content.Watanabe K., Masuda T., Ohashi H., Mihara H. & Suzuki Y. Multiple proline substitutions cumulatively thermostabilize Bacillus cereus ATCC7064 oligo-1,6-glucosidase. Irrefragable proof supporting the proline rule. ''Eur J Biochem'' 226,277-83 (1994).

References

Protein structure Thermodynamic entropy {{thermodynamics-stub

See also

References