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Updated: Jul 19, 2026

Modeling an Enzyme Active Site using Molecular Visualization Freeware
Published on: December 25, 2021
Comparative computational analysis of different active site conformations and substrates in a chalcone isomerase
J Javier Ruiz-Pernía1, Estanislao Silla, Iñaki Tuñón
1Departamento de Química Física, Universitat de València, 46100 Burjassot, Spain.
Abstract:
Chalcone isomerase catalyzes the transformation of chalcones to flavanones. We present a computational study of the rate-limiting chemical step, an intramolecular Michael addition of a 2'-oxyanion to the alpha,beta-double bound. By using quantum mechanical/molecular mechanical hybrid methods we traced the free-energy profiles associated with the reaction of two different substrates (chalcone and 6'-deoxychalcone) in two different conformations of the active site that are described in the different crystallographic structures available. We have obtained significant differences (about 4 kcal/mol) in the free-energy barriers calculated for the two active sites. According to our results, the active site conformation with larger catalytic power presents a positively charged lysine residue much closer to the substrate than the other. Complementary electronic and electrostatic analysis shows that the charge is transferred from the 2'-oxyanion to the beta-carbon atom. Interactions of the environment with these two atoms are essential to understand the differences between both active sites and also the origin of catalysis in this enzyme.
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