Molecular Mechanics Analysis of Molecular Recognition by Cyclodextrin Mimics of Alpha-Chymotrypsin

摘要

The method of molecular mechanics is used to investigate the structural and electrostatic features of molecular recognition by Beta-cyclodextrin and capped Beta -cyclodextrin models of alpha -chymotrypsin. Since capped Beta -cyclodextrin has been shown to be the more effective biomimetic catalyst, these features of molecular recognition can be interpreted in terms of the relationship between molecular structure and catalytic function. Calculations in vacuo show that the addition of an N-methyformamide cap substituent to each glucose unit appears to change the relative orientation of some glucose fragments from that found in the X-ray structure of the Beta -cyclodextrin macrocycle. These results indicate that certain structural components of molecular recognition, such as the orientation of the secondary hydroxyls and the related orientation of the caps, may be implicated in the catalysis. In addition, the electrostatic component of molecular recognition was investigated by the analysis of molecular electrostatic potential maps calculated in planes parallel to the average plane of the glycosidic oxygen atoms. the results indicate that the addition of the caps to the Beta -cyclodextrin macrocycle subtly alters the pattern of the maps in each plane. However, the general qualitative features of electrostatic recognition by Beta -cyclodextrin and capped Beta -cyclodextrin are similar. Keywords: Artificial enzymes, Enzyme models, Serine protease mimic. (aw)