Macromolecular receptor sites

A. R. Leach and I. D. Kuntz. Conformational analysis of flexible ligands in macromolecular receptor sites. Journal of Computational Chemistry, 13 730-748, 1992. 

Leach A R and I D Kuntz 1990. Conformational Analysis of Flexible Ligands in Macromolecular Receptor Sites. Journal of Computational Chemistry 13 730-748. 

Both the selection of classes of appropriate features, and how the bin distribution is accomplished, are the subjects of current research. One recent approach that holds promise is the expansion of 3D feature keys to include pharmacophoric or stereophoric features as surrogates for the macromolecular receptor site. Each of these features is comprised of a collection of three or four atomic environments (selected from a list including hydrogen-bond donors, acceptors, etc.) in association with interatomic distance ranges. Another theme is the introduction of a 3D surface descriptor as the basis for matching. 

Consider a macromolecular receptor, R, which contains n sites for the ligand L. Each site has the microscopic ligand association constant Kt for the /-site. 

Although structurally unrelated to the benzodiazepines, these drugs act on the same macromolecular receptor complex but at different sites from the benzodiazepines their effects can be blocked by flumazenil, the receptor antagonist. Those described below are all effective in insomnia, have low propensity for tolerance, rebound insomnia, withdrawal symptoms and abuse potential but there are few data of their effects in long-term studies. 

The specific correlations of functional groups with the chemical shifts of carbon and associated protons are always important tools for structure elucidation of simple sugars as well as complex oligosaccharides. The conformational behavior [65,66] of a particular disaccharide and oligosaccharide in solution is determined not only by intramolecular interactions but also by potential interactions that exist between the oligosaccharide and its environment. In particular, the nature of the solvent or more generally the environment in which the compound finds itself, can profoundly affect its geometry. Two such important factors, namely the fully solvated state (i. e. the molecule free in solution) and the molecule solvated by a macromolecular receptor (i. e. the molecule bound to the active site of the protein) contribute to the preferred conformation. 

Receptors are macromolecular binding sites for low molecular weight molecules (ligands), such as hormones and neurotransmitters. As such they are crucial to the well-being of the body. Xenobiotic ligands bind with receptors and in doing so interrupt the normal functioning of the body. 

A second application of the index is its use to predict candidate molecules to fill molecular cavities. With the increasing use of molecular graphics, the fit, docking, or intercalation of molecules into cavities in macromolecular simulations becomes an important consideration in drug design. The visualizations of proposed receptor sites, enzyme active sites, and other cavities and spaces of interest in macromolecules make it possible to make measurements of the dimensions of a cavity. Of course, the validity of these images depends on the quality of the input data and the assumptions attending the calculations. If the visualized details of a cavity are to be believed, then there is certainly some interest in what molecules may fit that cavity or some part of it. 

Models of parallel pseudo first-order reactions consider the case when two interactions with different rate constants proceed simultaneously. Such situations can be attributed to different kinds of receptor sites or to different states of the analyte [8,11]. In the first case the model can describe heterogeneity of the sensor surface the second may concern a macromolecular analyte that can be present in various conformations, protonation states, etc. Besides two sets of rate constants, the models also require specification of proportion p between the two fractions of the receptor or analyte. For the model considering two kinds of receptors, the following equations are obtained ... 

As already mentioned, no structure of a pharmacologically relevant receptor has so far been determined to atomic resolution. However, for the rational design of new biologically active ligands, information about the structures of these receptors is required. So far, various approaches have been developed for modeling receptor sites on the basis of structure/activity relationships [51]. If typical interaction patterns between small molecule ligands and macromolecular receptors were available, they... 

G. Sposito, On the use of the Langmuir equation in the interpretation of adsorption phenomena. II The two-surface Langmuir equation. Soil Sci. Soc. Am. J. 46 1147 (1982). See also I. M. Klotz, Numbers of receptor sites from Scatchard graphs Facts and fantasies. Science 217 1247 (1982). (In the literature of macromolecular chemistry, Fig. 4.2 is known as a Scatchard plot.)... 

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