Thermodynamic analysis of enzyme enantioselectivity: a statistical approach by means of new differential HybridMIF descriptors

The study of relationships between substrate structure and enzyme stereoselectivity was approached by means of a new molecular descriptor: the “differential Hybrid Molecular Interaction Field” (dH-MIF). The descriptor was conceived with the purpose of combining enthalpic and entropic information rel...

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Bibliographic Details
Published in:Biocatalysis and Biotransformation
Main Authors: FERRARIO, VALERIO, EBERT, CYNTHIA, GARDOSSI, Lucia, Foscato M.
Other Authors: Ferrario, Valerio, Foscato, M., Ebert, Cynthia, Gardossi, Lucia
Format: Article in Journal/Newspaper
Language:English
Published: 2013
Subjects:
enantioselettivity
entropy
lipase
computational chemistry
GRID
molecular descriptors
Hult
Antarc*
Antarctica
Online Access:http://hdl.handle.net/11368/2744901
https://doi.org/10.3109/10242422.2013.838025
Description
Summary:The study of relationships between substrate structure and enzyme stereoselectivity was approached by means of a new molecular descriptor: the “differential Hybrid Molecular Interaction Field” (dH-MIF). The descriptor was conceived with the purpose of combining enthalpic and entropic information related to enzyme–enantiomer interactions. The dH-MIFs were developed based on experimental data previously published by the group of Karl Hult on the enantioselectivity of the W104A mutant of lipase B from Candida antarctica, which is endowed with an enlarged stereoselectivity pocket. Because of the increased conformational freedom of substrates, the entropic contribution to enantiodiscrimination is particularly relevant in kinetic resolution of alcohols catalyzed by this enzyme. By combining molecular dynamic simulations and GRID analysis the new dH-MIF descriptors proved to be able to extract both enthalpic and entropic information from models of the tetrahedral intermediates of enantiomers.

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