Complementarity shape

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. 

Norel, R., Petrey, D., Wolfson, H. J., and Nussinov, R. (1999) Examination of shape complementarity in docking of unbound proteins. Proteins 36,307-317. 

Recentiy published crystal structures of antibody 4C6, an antibody that catalyzes another cationic cyclization reaction (Figure 6), revealed that this antibody has exquisite shape complementarity to its eliciting hapten 5. The active site contains multiple aromatic residues which shield the high-energy intermediate from solvent and stabilize the carbocation intermediates through cation-7r interactions. 

Figure 11.2. Globular conformations of an A-type duplex (left) and a B-type duplex (right), generally seen for RNA RNA and DNA DNA duplexes, respectively. Charge and shape complementarity of neomycin to the A-form major groove Computer models of (left) neomycin docked in the major groove of A-form DNA, and (right) neomycin buried in the B-form major groove. See color plates.

The earliest designers of scoring functions recognized two fundamental contributions to receptor-ligand complementarity shape and electrostatics. To account for 3D shape complementarity, they calculated some form of contact or van der Waals score, and to account for electrostatic interactions, they calculated some form of electrostatic potential score. In 1992 Kuntz and coworkers... 

L., Dixon, J. S., Rnntz, I. D., Venkataragha-van, R. (1988) Using shape complementarity as an initial screen in designing ligands for a receptor binding site of known three-dimensional structure. / Med Chem 31, 722-729. 

Figure 12 Conformation of statherin on HAp surface determined by molecular modelling. The four basic residues (K6, R9, RIO, and R13) fit nicely to the IPOT motif (outlined in dots). FADE scores are quantitative measure of shape complementarity. (Reprinted with permission from Ref. 181. 2007 American Chemical Society.)...

MIP catalyst 76 also performs enantioselective hydrolysis of non-activated d-and L-phenylalanine ethyl ester 78 at pH 7.4, with characteristic saturation kinetics (Scheme 13.19). While this catalyst does not have the precise shape complementarity to ester 78, a threefold enhancement compared to the blank reaction was observed. Furthermore, enantiodiscrimination was obtained, as compound 78 was hydrolyzed 1.44-fold faster than ent-78. Although the reported rate enhancement was modest compared to the standards in asymmetric synthesis, it can be considered as a first step in the development of imprinted polymers for enantioselective catalysts. 

The basic concepts of stereochemistry were independently developed by varft Hoff and Le Bel in 1874. Based on their findings Emil Fischer suggested that biological macromolecules are composed of chiral l amino acids and d sugars and in 1894 proposed his famous key and lock hypothesis that two chiral molecules interact through shape complementarity with each other and are therefore stereospecific [15]. 

Rapberger R, Lukas A, Mayer B (2007) Identification of discontinuous antigenic determinants on proteins based on shape complementarities. J Mol Recognit 20 113-121... 

Protein Docking Using Shape Complementarity, Electrostatics and Biochemical Information. 

The ability of enzymes to preorganize reactants for reaction contributes significantly to their efficacy [21]. The excellent shape complementarity observed in antibody-antigen complexes suggests that antibody binding energy could be exploited for this purpose. Antibody catalysts have been developed for bimolecular Diels-Alder reactions to test this supposition. 

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