Binding theoretical models

Long, G., J. McKinney, and L. Pedersen. 1987. Polychlorinated Dibenzofuran (PCDF) Binding to the Ah Receptor(s) and Associated Enzyme Induction. Theoretical Model based on Molecular Parameters. Quant. Struct.-Act. Relat. 6, 1. 

A theoretical analysis is presented for the binding of the four dia-stereoisomers of benzo[a]pyrene diol epoxides (BPDEs) to N2(g), N6(a), 06(G) and NU(c). Molecular models for binding and stereoselectivity involving intercalation, intercalative covalently and externally bound forms are presented. Molecular mechanics calculations provide the energetics which suggest possible structures for the formation of each of the principal DNA-BPDE complexes. Stereographic projections are used to illustrate the molecular structures and steric fits. The results of previous calculations on intercalation and adduct formation of BPDE l(+) in kinked DNA (37) are summarized and extended to include the four diastereoisomers l( ) and II( ). The theoretical model is consistent with the observed experimental data. 

As regards the first aspect, the properties reported in Tables 5.1 and 5.2 have to be considered. Combining the right structural and physicochemical elements should result in appropriate suggestions on howto avoid the possibility that a new drug binds to and blocks the hERG channel. Only the practical application of such suggestions by medicinal chemists will allow to assess the correctness of the indications, but several examples collected by Jamieson et al. [44] already exist and seem to be consistent with the output of the theoretical models listed in Tables 5.1 and 5.2 (see also Chapter 17). 

D. E. Koshland, G. Nemethy, and D. Filmer, Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 5(1), 365 368 (1966). 

Several predictions of this model have been experimentally supported, including the estimated heme-heme distance, and the protection of various (charged) groups on cytochrome c and ccp. However, as already noted, other theoretical models have suggested that multiple binding sites are possible within the cyt c ccp complex. The available spectroscopic and crystallographic data, reviewed in this section, tend to support a multisite model, rather than a highly specific lock and key structural model. 

Altered thermodynamic activity of proteins in solution arises when unreactive (or inert) macromolecules are added to a solution and occupy more than a few percent of total solution volume. Terms such as unreactive , "background, or inert are used to emphasize that the added protein need not exhibit and direct binding interaction with the protein of interest. Instead, the consequences have more to do with molecular crowding, and approximate theoretical models show that this effect depends on the shapes and sizes of the macromolecules. Thus, biological fluids are anything but ideal or dilute solutions. 

We shall examine briefly the photoemission (XPS) binding energies (Et, relative to Ep) of core levels for open shell metals. An ample discussion has been developed in this matter, leading to a satisfactory agreement between theoretical models and experimental spectroscopic results. For the purpose of this book, the theoretical model employed is relevant... 

The scorpion a-toxins have been shown to bind to site 3 on the voltage-gated sodium channel [24,27,42]. These polypeptides contain up to 70 residues crosslinked by four disulfide bonds, but show no sequence similarity to the anemone polypeptides. Possible structural similarities have been discussed [24], and in a theoretical model of the anemone toxin Bg II, some of the cationic residues were in similar locations to those in the crystal structure of the scorpion toxin Aah II [26]. 

The binding of fluorescent probes of different hydrophobicities can be used to compare the surface properties of proteins in relation to their physicochemical properties, such as foaming and emulsifying. CPA (cfr-parinaric acid) has been used to study eleven food-related proteins, and the results have been compared with theoretical models for predicting foam capacity (Arteaga and Nakai, 1993 also see... 

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