Electrostatic features of molecular recognition by cyclic urea mimics of chymotrypsin

Document Type

Article

Publication Date

1-1-1988

Abstract

The molecular electrostatic-potential pattern was used to investigate the electrostatic features of molecular recognition by two cyclic urea mimics of the active site of α-chymotrypsin. The structures of the mimics were obtained by molecular-mechanics evaluation of the conformational potential-energy surface of the molecules. Calculations were done by using two different atomic point-charge sets in order to assess the effect of charge on the electrostatic potential pattern. The molecules studies were: (1) a "full" mimic of chymotrypsin containing the hydroxyl, imidazole, and carboxylate anion functionalities typical of the active site of the enzyme, and (2) a "partial" mimic with only the hydroxyl and imidazole functional groups. Comparison of the molecular electrostatic-potential patterns of the two mimics in both charge sets showed that the largest differences were due to the structural addition of the carboxylate anion, rather than any particular differences in the choice of atomic point charge. For the full mimic, the pattern was essentially dominated by the negative charge on the carboxylate. Small structural changes which optimized the orientation of the catalytic components had little effect on the electrostatic potential pattern of the molecule. In the absence of the anionic functionality, greater differences were noted in the electrostatic potential pattern of the partial mimic in the two charge sets. The choice of atomic point charge was seen to influence the hydrogen-bonding pattern of the hydroxyl and imidazole moieties, resulting in differences in the spatial orientation of the electrostatic potential minima. In general, both charge sets produced molecular electrostatic-potential patterns which indicated that long-range electrostatic interactions would direct the cationic end of the substrate into the electron-rich binding site. However, specific local features of the electrostatic potential pattern were found to depend on point-charge set through the influence of charge on the hydrogen-bonding pattern. © 1988.

Identifier

0023683191 (Scopus)

Publication Title

Analytica Chimica Acta

External Full Text Location

https://doi.org/10.1016/S0003-2670(00)83887-8

ISSN

00032670

First Page

151

Last Page

162

Issue

C

Volume

210

Grant

CPE-8404363

Fund Ref

National Science Foundation

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