Grooves entropy

In section 2.1 the contact interface between TBP and the minor groove of DNA was characterized as anhydrous. This is a common characteristic in all the TBP-DNA complexes available to date. As TBP presents a primarily hydrophobic surface to DNA, most of the hydrogen bond donors and acceptors at this surface are not satisfied by the complexation. Hence, there is likely to be an enthalpic penalty associated with the dehydration of this surface. This penalty is compensated by the favorable increase in entropy associated with the liberation of the surface-bound water molecules into bulk solution. Following this reasoning, there are two aspects of hydration that could contribute to the determination of sequence specificity the ideal sequence would be one which coordinates a large number of water molecules, but binds them least tightly. 

One useful discriminator of structure and dynamics in liquid is obtained through entropy. However, experimental or theoretical estimation of the entropy of a liquid confined to a local region is quite hard. This has hampered our understanding of the order/disorder transition in the local region at the mesoscopic length scale. One such rare study concentrated on the estimation of the entropy of water molecules in the groove region and correlated with the observed dynamics. Note that calculation of... 

As mentioned earlier, it is difficult to obtain a quantitative measure of entropy. By using the 2PT method (the method will be described later in Chapter 19), one can obtain the entropy of water molecules in both major and minor grooves of DNA. One can also get a measure of the translational diffijsivity of those water molecules from the mean-square displacement or velocity autocorrelation function - all these are fortunately easily available with computer simulations. 

Another interesting aspect of this observation relates to another celebrated equation, the Stokes-Einstein relation between diflfirsivity and viscosity. It tells us that one can now define the viscosity in a nano-confined region (grooves of DNA), which is termed the microviscosity of that particular region [7]. The Stokes-Einstein relation, where the translational diflfirsion constant and viscosity are inversely related, provides a remarkable correlation between microviscosity and configurational entropy. 

Hydration of the grooves is particularly relevant for AT minor grooves because the groove is both narrow and deep. Water molecules are known to form a spine of hydration along the minor grooves. Recent computer simulation studies have quantified the nature of the spine of hydration by using concepts from bulk water. Thus, one has used the tetrahedrality order parameter to demonstrate that the water molecules are indeed partly ice-like. The entropy calculation has further substantiated these observations. 

Entropy of water in confined systems (reverse micefies, carbon nanotubes, grooves of DNA)... 

PBD-benzimidazole conjugates also binds in the DNA minor groove with a paeference for (A,T)4G sequences. Whereas the binding of both ligands is enthalpy-driven and associated with a negative entropy, the benzimidazole hybrid exhibits a less favourable binding enthalpy that is counterbalanced by a more favourable entropic term when comprared to the naphthalimide hybrid. ]... 

Circular dichroism is largely employed to investigate interactions among different biomolecules (protein-protein, protein-nucleic acid, etc.), and among biomolecules and other ligands (for examples, molecules of medicinal interest). Also in this case, not only thermodynamic (association constants, reaction enthalpy and entropy) and kinetic (reaction rates and activation barriers) parameters can be determined, but also different association modes (e.g., DNA intercalation or association in the minor or major groove of the double helix) can be distinguished. Finally, CD spectroscopy is applied in analytical sciences to determine the purity of optically active compounds. 

---