AVERAGE binding energies of representative amino acid residues

Range Table - link
Organism Generic
Reference Andrews PR, Craik DJ, Martin JL. Functional group contributions to drug-receptor interactions. J Med Chem. 1984 Dec27(12):1648-57.PubMed ID6094812
Method Table gives the AVERAGE binding energy for a series of representative amino acids within a polypeptide molecule (i.e., calculated from the intrinsic binding energies in Table - link without allowing for charged carboxyl or amino terminals). The AVERAGE binding energy of a cyclic peptide can be calculated simply by summing the individual binding energies of the component amino acids and subtracting the 14 kcal/mol allowance for loss of overall rotational and translational entropy. The calculation for noncyclic peptides is similar, except that a further 15.1 kcal/mol must be added to account for the charged terminal groups. In the case of large peptides such as insulin, this calculation clearly results in massive AVERAGE binding energies.
Comments AVERAGE=Average Energy Resulting from All Group Energies. To answer questions concerning drug-receptor binding enegies, there is need to have some way of estimating the potential bond strengths involved in the interaction between a drug and a reasonably matched receptor, but mechanisms for providing such estimates are presently far from satisfactory. It is possible, for example, to calculate the strengths of intermolecular interactions at various levels of approximation, using perturbation theory, but such calculations are not only time-consuming and inaccessible to the majority of workers but also quite unreliable in aqueous solution. For these reasons, most medicinal chemists prefer the simpler alternative of using standard values of the enthalpies of formation for different types of bond (ionic, hydrogen, van der Waals, etc.) to estimate approximate strengths for drug-receptor interaction. Again, however, there are problems with this approach, including particularly the lack of any allowance for the entropic component of the interaction, the relatively large range of energies associated with each type of bond, and the uncertainty as to which of the possible bonds associated with any drug should be included in the interaction. To overcome these difficulties, efforts have been made to estimate the strengths of interactions involving individual functional groups of the drug. One approach, which relies on finding pairs of compounds for which the difference in binding to a receptor or enzyme may be traced solely to the contribution of a single functional group, has been developed by Page and Jencks (refs 5,6 in article), who refer to it as the anchor principle. It has the major advantage that the difference in binding of a drug molecule with, and without, the particular functional group, incorporates only the factors associated with that group while excluding the loss of overall rotational and translational entropy associated with the drug molecule (the anchor).It is limited, however, by the requirement for many pairs of compounds that differ only in the presence of a single functional group and in which the role of that functional group can be traced more or less exclusively to the provision of additional binding energy, rather than, for example, to conformational enhancement of biologically active forms. In the present paper, researchers have attempted to overcome this limitation by using a series of 200 drugs and enzyme inhibitors, chosen somewhat subjectively on the basis of their apparent tight binding to their corresponding receptor sites, to provide a statistical estimate of the strengths of noncovalent bonds associated with each functional group in an average drug-receptor environment. See BNID 105018,105020
Entered by Uri M
ID 105019