Drug-receptor interactions, hydrogen

Mathematical models are the link between what is observed experimentally and what is thought to occur at the molecular level. In physical sciences, such as chemistry, there is a direct correspondence between the experimental observation and the molecular world (i.e., a nuclear magnetic resonance spectrum directly reflects the interaction of hydrogen atoms on a molecule). In pharmacology the observations are much more indirect, leaving a much wider gap between the physical chemistry involved in drug-receptor interaction and what the cell does in response to those interactions (through the cellular veil ). Hence, models become uniquely important. 

Thus, non-covalent hydrophobic interactions, hydrogen bonds, and electrostatic bonds all contribute to the overall shape of a protein (Figure 13.3). As we shall see (Section 13.3.2), many pertinent properties of a protein are then provided by the appropriate combination of the remaining amino acid side-chains that reside on the surface, allowing specific binding to various molecules. This is the essence of enzymic activity and drug-receptor interactions. 

Electrostatic bonding is much more common than covalent bonding in drug-receptor interactions. Electrostatic bonds vary from relatively strong linkages between permanently charged ionic molecules to weaker hydrogen bonds and very weak induced dipole interactions such as van der Waals forces and similar phenomena. Electrostatic bonds are weaker than covalent bonds. 

The ability of the pharmacophore method to identify and focus on features important for drug-receptor interactions was important for this result for example, the assignment of the acidic feature to the acylsulfonamide group increases the overlap by about a third (acids were also considered as general hydrogen-bond acceptors for this analysis). 

In the broadest sense, these "bonds would include covalent, ionic, hydrogen, dipole-dipole, van der Waals, and hydrophobic interactions. Most drug-receptor interactions constitute a combination of the bond types listed in Table 1.1, most of which are reversible under physiological conditions. 

Hadzi, D., Kidric, I, Koller, J. and Mavri, J. (1990). The Role of Hydrogen Bonding in Drug-Receptor Interactions. J. Mol. Struct., 237,139-150. 

According to the equation (21.2), ligand-receptor interactions are characterized by enthalpy-entropy compensation in which one term favors and the other disfavors binding. While enthalpic contributions include electrostatic, hydrogen bond, and Van der Waals interactions, entropic contributions arise from several sources. On one hand, the loss of flexibility upon binding has an important entropic cost, counterbalanced on the other hand by the displacement of ordered water molecules. This will be discussed in the next section as well as the various types of drug-receptor interactions. 

Among the numerous examples of drug-receptor interactions through hydrogen bonds, the antibiotic vancomycin... 

---