Electrostatic complementarity

Specificity for a particular charged substrate can be engineered into an enzyme by replacement of residues within the enzyme-active site to achieve electrostatic complementarity between the enzyme and substrate (75). Protein engineering, when coupled with detailed stmctural information, is a powerful technique that can be used to alter the catalytic activity of an enzyme in a predictable fashion. 

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. 

In terms of enzyme catalysis, the following factors are likely to influence the magnitude of the rate enhancement in enzymatic processes (a) proximity and orientation effects (b) electrostatic complementarity of the enzyme s active site with respect to the reactant s stabilized transition state configuration (c) enzyme-bound metal ions that serve as template, that alter pK s of catalytic groups, that facilitate nucleophilic attack, and that have... 

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

Kangas, E. and Tidor, B. (2001) Electrostatic complementarity at ligand binding site application to chorismate mutase, J. Phys. Chem. 105, 880-888. 

Electrostatic complementarity between the enzyme and its ligand is illustrated on the example of the binding of the Lys-15 side chain of bovine pancreatic trypsin inhibitor (BPTI) to the specificity pocket of trypsin (Figure 4.). The MEP of BPTI which is displayed on the van der Waals envelope of the Lys side chain is complementary to that displayed on the same surface but emerging from the enzyme... 

The typical protocol for a docking experiment first involves the generation of a large set of putative complexes covering as many conformations as possible at a given resolution level (e g., defined by the minimal angle for the orientation of the two structures). This collection of potential solutions is then analyzed in terms of their energies and a simple evaluation of the electrostatic complementarity. 

McCoy AJ, Chandana Epa V, Colman PM (1997) Electrostatic complementarity at protein/ protein interfaces. J Mol Biol 268(2) 570-584... 

Figure 3. Surfaces of TNT and polymer structures, illustrating the shape and electrostatic complementarity between triphenylene and TNT. The lighter regions represent negative charge and the darker regions represent positive charge.

Figure 2. The chemical structure of an AFP and the electrostatic complementarity of an AFP receptor site to TNT.

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