Relative binding affinity

The critical factor for any method involving an approximation or an extrapolation is its range of application. Liu et al. [15] demonstrated that the approach performed well for mutations involving the creation or deletion of single atoms. The method has also been successfully applied to the prediction of the relative binding affinities of benzene, toluene and o-, p-, and m-xylene to a mutant of T4-lysozyme [16]. In both cases, however, the perturbation to the system was small. To investigate range over which the extrapolation may... 

Fig. 11.6 The SC24/halide system. (Figure adapted from Lybrand T P, ] A McCammon and G Wipff 1986. Theoretical Calculation of Relative Binding Affinity in Host-Guest Systems. Proceedings of the National Al adeniy of Sciences USA 83 833-835.)...

Table 2. Thyromimetic Compounds Relative Binding Affinities (BA) and Antigoiter Potencies (AG)...

Using any of the carrier proteins available in highly purified form, eg, TBG or TBPA, a convenient and accurate quantitative determination of and is possible by displacement of radioiodinated or T. This procedure enables their quick determination at low concentrations even in the presence of coundess other substances that occur in body duids (31). In a similar fashion, intact cell nuclei or solubilized proteins from rat fiver cell nuclei, which display high affinities for thyroid hormones, especially T, have been used to establish relative binding affinities of many thyromimetic compounds (7). 

It is often the case that alchemical transformations are used to compare the binding affinity of two ligands and Jz 2 to a receptor molecule R. For example Jz i and -S 2 might be two putative inhibitors of an enzyme R. If AA (respectively, AA2) is the free energy of binding (respectively, Jz 2) to R, we can define the relative binding affinity by AAA = AA2 — AA4. 

Swaan, P. W., Stenhouwer, M. C., Tukker, J., Molecular mechanism for the relative binding affinity to the intestinal peptide carrier. Comparison of three ACE-inhibitors enalapril, enalaprilat, and lisinopril, Biochim. Biophys. Acta 1995, 3236, 31-38. 

Maeda, H., Fujita, N., and Ishihama, A. (2000) Competition among seven Escherichia coli subunits Relative binding affinities to the core RNA polymerase. Nucleic Acids Res. 28, 3497-3503. 

Solid-phase synthesis of dihydropteridinones has been achieved from 4,6-dichloro-5-nitropyrimidine <00TL8177>. A series of ethyl 7-aminopteridine-6-carboxylate derivatives has been prepared in one step from the reaction of vicinal diamines as 13-dialky 1-5,6-diamino-2-thiouracils with diethyl ( )-2,3-dicyanobutenedioate <99JHC1317>. The relative binding affinities to human dihydrofolate reductase of new 2,4-diaminopteridine derivatives... 

S. B. Singh, Ajay, D. E. Wemmer, and P. A. Kollman, Relative binding affinities of distamycin and its analog to d(CGCAAGTTGGC).d(GCCAACTTGCG) Comparison of simulation results with experiment, Proc. Natl. Acad. Sci. 91 7673 (1994). 

Scanning Results vs. Experimental Relative Binding Affinities... 

Similarly, differences for the binding affinity of AMP for the AMP binding site of wild-type FBPase vs. mutant FBPase were calculated and compared with experimental data derived from the ratio of the corresponding IC50s. The calculated results generated from the scan were compared with the experimentally-determined relative binding affinities and reported in our earlier communication.13... 

The FEP method has shown good accuracy when used to determine the relative binding affinity for two structurally-related ligands. Unfortunately, the newly designed analogues requested by medicinal chemists frequently represent large structural changes from the lead compound and therefore are not well suited for the FEP method. 

---