Ligand binding geometric fits

Figure 8.1. Lock and key model (a) geometrical fit, (b) complementary pattern of functional groups, (c) site preference due to the solvent effect. The ligand L may better fit site A, but it binds preferentially to site B due to the solvent effect...

Consider Fig. 8.17 where we have two identical sites A and B. From the point of view of the lock and key model, the ligand L would have exactly the same probability to bind to either A or to B. In Fig. 8.17 we have depicted a perfect geometrical fit between the ligand and the sites, but the same argument will hold if the fit is produced by a complementary pattern of FG. The important point is that the sites A and B provide the same binding energy to the hgand L. 

The second generalization, developed mainly by Koshland, is based on the recognition that enzymes (like any protein) have a multitude of conformations at equilibrium. Since the ligand is likely to interact differently with the various conformations, one can expect a shift in the distribution of conformations induced by the binding process. This is the induced fit model. It states that the best fit (by either geometrical or by a complementary pattern) does not necessarily exist before... 

The work summarized here fits into the broad subject of molecular inclusion chemistry [1-5]. Cavities in molecules are tailored electronically and geometrically to the chemical purpose at hand. In simple systems, the goal might be selective coordination of metal ions or selective binding of small ligands to previously coordinated metal ions. 

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