Intrinsic binding energies of several functional groups

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 The binding constants and structural components of 200 drugs and enzyme inhibitors have been used to calculate the average binding energies of 10 common functional groups. As expected, charged groups bind more strongly than polar groups, which in turn bind more tightly than nonpolar groups. In regression analyses for which the intercept has been arbitrarily fixed (in this case, to a known value), standard statistical parameters for evaluating the fit (e.g., the multiple correlation coefficient) and for determining the accuracy of derived regression coefficients (e.g., t tests) are not meaningful. An alternative measure of the accuracy of researchers' intrinsic binding energies (coefficients in eq 4 in article) was therefore obtained by running regression analyses on random subsets of the initial 200-compound data base to monitor variations in the derived coefficients. The ranges of Ex (Intrinsic binding energy) values for six separate sets of 100 compounds are shown in Table. In terms of percentage errors, the smaller coefficients are less well defined than the larger values, but, in general, the ranges in Ex are fairly small. The values in Table 2 are certainly more tightly defined than have been previous estimates of intrinsic binding energies.
Comments The derived intrinsic energies may be used to determine the goodness of fit of a drug to its receptor. This is done by comparing the observed binding constant to the average binding energy calculated by summing the intrinsic binding energies of the component groups and then subtracting two entropy related terms (14 kcal/mol for the loss of overall rotational and translational entropy and 0.7 kcal/mol for each degree of conformational freedom). See BNID 105019-105020
Entered by Uri M
ID 105018