Thermodynamics is a very important subject in physical science, which focus mainly on mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). Macroscopically, statistical mechanics explained the laws of thermodynamics. Thermodynamics applies to a wide variety of topics in biochemistry, science, and engineering, especially physical chemistry, chemical engineering and mechanical engineering.
Accordingto the hypothesis of thermodynamics in biochemistry, the random coiled form of the protein is most favorable conformation for any protein, because it permits the highest degree of dissorderness. If any protein required to get particular structural level conformation, first it should compensate for the enthalpy of the reaction. The explanation of this concept has been clearly described below
∆G for a process depends on ∆H, ∆S and temperature [T]
∆G= Free energy change
∆H= enthalpy change
∆S= entropy change
Considering the above formula. If enthalpy (ΔH) is positive, the reaction is endothermic, which means heat is absorbed by the reaction because the products of the reaction having a more enthalpy than the reactants. In another case, if ΔH is negative, the reaction is exothermic, which means the overall enthalpy decrease is achieved by the generation of heat.
For example: If we discuss the enzyme reaction, the process can be two types
Endothermic reaction: If any enzyme required energy to perform the reaction, which means the final product of the reaction is having more enthalpy than the substrate, hence for the reaction to happen, we should provide the energy. In this process, energy or heat will be absorbed.
Exothermic reaction: If any enzyme performs the reaction without additional energy which means the final product of the reaction is having less enthalpy than reactants. In this process heat or energy will be released to surroundings.
Hence, for any reaction to perform, the value of the free energy should be negative (-∆G). The proteins in random coiled form have more entropy (∆H) than any other structure of the protein. Which means, higher entropy (randomness or disorder) of the protein provides always favorable conditions unless a greater negative enthalpy value can compensate for the loss in entropy. The increase in enthalpy can be obtained from interactions such as hydrogen bonding, van der Waals forces, hydrophobic interaction and dipolar interactions (Salt bridges). According to sheer absolute values of enthalpy, the significant increase of enthalpy is obtained from hydrogen bonding than other interactions in protein folding. If we observe the process of protein folding, the initial interaction between two peptide bonds reduces the randomness of the polypeptide strand which is mainly by the formation of a hydrogen bonds.
As above mentioned, in a randomly coiled polypeptide strand, the level of entropy is more and enthalpy is less compared to a higher-ordered structure (condensed). Also, the solvent present around the protein forms hydrogen bonds with the moieties in the protein backbone. Once the folding initiated, the intermolecular hydrogen bonds will be formed by a gain in structure and it should compensate both for the loss in entropy and the loss of hydrogen bonds with the solvent.
During alpha-helix formation, initially, the linear polypeptide chain forms a single hydrogen bond between carboxyl oxygen of i th amino acid and imino hydrogen of i+ 4th amino acid to form one turn, it leads to initial changes in orientation of 6 torsion angles (α, β and ω) in the polypeptide chain. Formation of additional turn to this initial nucleation site requires only orientation of three torsion angles by hydrogen bonding. Thus, it is more favorable to add turns of a helix to an initial nucleation site and this is described as a cooperative effect in helix formation.
Due to the cooperative effect, the formation of further turns more likely follow the order established in the previous step. Formation of helical structure follows exactly this one. The periodicity of fold-formation can arise from sequential interactions in α- helix or long-distance sheet formation in β- plated sheets.