Molecular recognition by artificial enzymes: Cyclic urea mimetics of alpha chymotrypsin

Document Type

Article

Publication Date

1-1-1985

Abstract

Molecular mechanics calculations are used to investigate the degree of structural preorganization and electrostatic complementarity for substrate binding exhibited by the cyclic urea mimetics of alpha chymotrypsin. The Amber molecular mechanics force field is used to calculate the “native” and complexed structures of a cation‐binding mimetic precursor compound, as well as the structure of the cyclic urea compound containing an m‐methylenehydroxy phenyl substituent, which mimics the action of the serine 195 residue in alpha chymotrypsin. Comparison of the native and complexed structures of the cation‐binding precursor compound shows that this cyclic urea compound undergoes little conformational change upon substrate binding. Addition of the m‐methylenehydroxy phenyl group is found to have little effect on the conformation of the macrocycle. Molecular electrostatic potential maps calculated in planes parallel to the average plane of the oxygen atoms of the macrocycle indicate that the orientation of the oxygen atoms directs the cationic end of the substrate into the electron‐rich center of the macrocycle. The m‐methylenehydroxy phenyl substituent affects the electrostatic potential pattern by pulling some of the electron density away from the center of the macrocycle. Similar structural and electrostatic comparisons are made with models of the active site of alpha chymotrypsin taken from the X‐ray data. Copyright © 1985 John Wiley & Sons, Inc.

Identifier

84987058255 (Scopus)

Publication Title

International Journal of Quantum Chemistry

External Full Text Location

https://doi.org/10.1002/qua.560280709

e-ISSN

1097461X

ISSN

00207608

First Page

69

Last Page

87

Issue

12 S

Volume

28

This document is currently not available here.

Share

COinS