Thermodynamic bases of protein structural elements and DNA
In terms of thermodynamics, the enthalpy is a measure of the change in heat associated with binding, whereas the entropic factor reflects a change in disorder of the system. One of the intriguing topics in the field of energetics of biological macromolecules is what forces (enthalpic or entropic) stabilize the structure of important biological macromolecules (α-helix in proteins and DNA). It is believed that hydrogen bonds stabilize the DNA duplex and the alpha helix due to enthalpy
The α-helix is the first regular conformation of the polypeptide chain to be recognized. It is held together largely by hydrogen bonds (see Figure 1). In the disordered state of the polypeptide chain the groups participating in this intramolecular H-bond are expected to be hydrogen bonded to water molecules, so it was difficult to envisage the source of any enthalpic stabilization of the helix from H-bonding. In contrast, formation of the helix must be accompanied by the shedding of water molecules from the amino and carbonyl groups into the bulk solvent, resulting in a substantial entropy increase. So what is the evidence that in aqueous solution intramolecular hydrogen bonds are entropic rather than enthalpic interactions?
With the definition of the DNA double helix it appeared that its regular structure is also maintained by hydrogen bonding, in this case between the conjugate base pairs: A with T and G with C (see Figure 1).
To make comparison between the two structures and driving forces of their stability the thermodynamic signatures of both the α-helix and the DNA duplex should be investigated.
Enthalpies and entropies of forming the base pairs of the DNA duplex and the α-helix at 25oC are shown below (Figure 2). Enthalpies in red. The total entropy factor (in green) is made up of a large reduction in conformational entropy (ΔSConformational in cyan) and an increase in entropy from water release on forming the H-bonds (in dark blue).
The preliminary results obtained by the microcalorimetry and optical methods have shown that despite very different structures between α–helix and DNA duplex, the thermodynamic basis of their stability are strikingly similar. The general conclusion follows that the stability of protein folds is primarily dependent on internal atomic close contacts and not on the network of hydrogen bonds they contain.
Computer modelling and experimental investigations of biological nanocomposite complexes. 2016-2108
Dragan A., Crane-Robinson, C. Privalov, P.L. (2021). Thermodynamic basis of the α-helix and DNA duplex/ European Biophysics Journal, 2021, 50(5), 787–792
Dragan A., Privalov, P.L., Crane-Robinson, C. (2019). Thermodynamics of DNA: heat capacity changes on duplex unfolding. Eur. Biophys. J. 48, 773-779.
Dragan, A.I., Read, C.M., Crane-Robinson, C. (2019) Hydration differences between the major and minor grooves of DNA revealed from heat capacity measurements. European Biophysics Journal, 2019, 48(2), 131–138
Dragan, A.I., Frank, L., Liu, Y., Makeyeva, E.N., Crane-Robinson, C., Privalov, P.L. (2004a). Thermodynamic signature of GCN4-bZIP binding to DNA indicates the role of water in discriminating between the AP-1 and ATF/CREB sites. J. Mol. Biol. 343, 865-878.
Dragan, A.I., Potekhin, S.A., Sivolob, A., Lu, Ï Privalov, P.L. (2004b)
Kinetics and Thermodynamics of the Unfolding and Refolding of the
Three-Stranded Helical Coiled Coil, Lpp-56. Biochemistry, 43, 14891-14900.
Dragan, A.I., Read, C.M., Makeyeva, E.N., Milgotina, E.I., Churchill, M.E., Crane-Robinson, C., Privalov, P.L. (2004c). DNA binding and bending by HMG boxes: energetic determinants of specificity. J. Mol. Biol. 343, 371-393.