Steric complementarity

V n der W ls Interactions. Van der Waals iateractions result from the asymmetric distribution of electronic charge surrounding an atom, which induces a complementary dipole in a neighboring atom, resulting in an attractive force. In general, the attractive force of van der Waals interactions is very weak (<4.2 kJ/mol (1 kcal/mol)) but may become significant if steric complementarity creates an opportunity to form a large number of van der Waals attractions. 

In conclusion, one important factor that contributes to the strong affinity of TBP proteins to TATA boxes is the large hydrophobic interaction area between them. Major distortions of the B-DNA structure cause the DNA to present a wide and shallow minor groove surface that is sterically complementary to the underside of the saddle structure of the TBP protein. The complementarity of these surfaces, and in addition the six specific hydrogen bonds between four side chains from TBP and four hydrogen bond acceptors from bases in the minor groove, are the main factors responsible for causing TBP to bind to TATA boxes 100,000-fold more readily than to a random DNA sequence. 

Intermolecular recognition and self-assembly processes both in the solid, liquid, and gas phases are the result of the balanced action of steric and electronic factors related to shape complementarity, size compatibility, and specific anisotropic interactions. Rather than pursuing specific and definitive rules for recognition and self-assembly processes, we will afford some heuristic principles that can be used as guidelines in XB-based supramolecular chemistry. 

In each structure, the assembled components satisfy the chemical descriptors specified while maintaining steric and electrostatic complementarity with the active site. The functional groups (in bold) interact with the receptor pharmacophoric elements as described in Figure 8.16. 

The recognition of a receptor function is the practical manifestation of successful receptor design. It follows that synthetic molecular receptors, in common with their natural counterparts, must be capable of recognizing other chemical species by achieving complementarity of steric and electronic shape, as well as, of course, size. 

It will be seen below that various types of information may be stored in a molecule thus, complementarity amounts to a sort of generalized "lock and key relationship not limited to steric fit of L and S, but extending over other molecular features. 

The affinity of a substrate with its biological target is first connected to its complementarity with this macromolecule target. The molecular recognition and affinity depend on all the favorable interactions that exist in the supramolecular assembly formed between the substrate and the macromolecule. If the presence of fluorine atoms enhances the strength or the number of these favorable interactions, the affinity of the fluorinated substrate will be higher than that of the parent compound. The main parameters involved are the steric and conformational effects, the dipolar/hydrophobic interactions, and the hydrogen bonds. 

Drug-receptor interaction depends on optimal steric and electrostatic complementarity of their combining surfaces. Quantification of the binding... 

Unfortunately, the outcome of oxidation is not only dependent on the ease with which it will occur (susceptibility) but is also dependent on the overall lipophilicity of the molecule (see Section 2.3.1). The enzymes most frequently implicated in the transformation of compounds to reactive toxins are the cytochrome P450s. Because the determinants of binding (lipophilicity, steric complementarity, presence of polar functions) vary in importance across the various P450 isoenzymes, the outcome of metabolism is currently much more difficult to predict than the susceptibility. 

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