Receptor and substrate interactions

Receptor and substrate are terms describing the species involved in complex formation. Throughout the chapter the receptor will refer tp the macrocyclic ligand, the substrate to other interacting species. Substrates may be metal or molecular catibns, neutral molecules, or atomic or molecular anions. The terms receptor and substrate imply that the complex formed has the well-defined structural and chemical properties of a supermolecule, as in biological receptor-substrate associations. They exclude species formed only in the solid state (clathrates). They are also easily converted and understood in many languages. 

Fig. 11.14. Schematic illustration of a COSMO-RS-based scoring function. Starting from the known surface polarities, a and a, of nearby receptor and substrate surfaces, the interaction energy could be evaluated using the COSMO-RS expressions for misfit and hb energies.

These qualitative assays show that one-armed cationic guanidiniocarbonyl pyrrole receptors can indeed effectively bind tetrapeptides even in water. Molecular modeling studies suggest a complex structure as shown for one specific example, the receptor Val-Val-Val-CBS, in Figure 2.3.11. Receptor and substrate form a hydrogen bonded //-sheet which is further stabilized by additional hydrophobic interactions between the apolar groups in the side-chains. Recognition of the tetrapep-tide thus seems to be controlled by a fine balanced interplay between electrostatic and hydrophobic interactions. 

The example above fits well the most general rule of molecular recognition science the higher number of the interaction points between receptor and substrate, the higher the selectivity. However, it is possible to achieve specific recognition of a... 

GRGDS the resonance frequency does not indicate any cell adhesion to the resonator surface. In contrast, when SDGRG is added to the culture fluid, there is no difference compared to experiments in which no peptide is present at all (compare Fig. 2a). Thus, when specific interactions between cell-surface receptors and substrate-immobilized proteins are not allowed to form, we do not observe any measurable impact on QCM readings. Apparently, loose attachment of the cell bodies to the substratum does not produce any significant acoustic load [12,16]. 

While hydrophobicity is (whatever its origin) certainly an important force that guides the recognition of a protein and its substrate, water seems also to be important for the interaction of hydrophilic regions of such complexes. Around 70% of interfacial residues are in fact hydrophilic. It is common to assume that such polar groups experience a direct electrostatic interaction mediated by the (continuum) solvent. But in fact the water network has a more complex role here too. For example, in the formation of the complex between the bacterial ribonuclease bamase and its inhibitor barstar, water molecules mediate and stabilize the hydrophilic interactions between receptor and substrate at the granular level [60]. 

Fig. 1. Schematic representation of a receptor—substrate (host—guest) complex involving cavity inclusion of the substrate and the formation of different types of weak supramolecular interactions between receptor (hatched) and substrate (dotted).

The weak intemiolecular forces that are principally involved in stabilizing receptor-substrate interactions and involved in molecular recognition processes (16) are summarized in Table 2. Examples are shown in Figure 1. 

TT-stacking and charge-transfer interaction between aromatic residues in the receptor and delocalized regions of the substrate van der Waals attraction between hydrophobic regions on the two components... 

Most effective differentiation of the receptor between substrates will occur when multiple interactions are involved in the recognition process. The more binding regions (contact area) present, the stronger and more selective will be the recognition (17). This is the case for receptor molecules that contain intramolecular cavities, clefts or pockets into which the substrate may fit (Fig. 1). 

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