How important is the synclinal conformation of sulfonylureas to explain the inhibition of AHAS: A theoretical study

Gonzalo A. Jaña, Eduardo J. Delgado, Fabiola E. Medina

Resultado de la investigación: Article

3 Citas (Scopus)

Resumen

The inhibitory activity of 15 sulfonylureas on acetohydroxyacid synthase (AHAS) is addressed theoretically in order to stress how important the conformation is to explain their differences as AHAS inhibitors. The study includes calculations in gas phase, solution, and in the enzymatic environment. The results suggest that both the activation Gibbs free energy and Gibbs free energy change associated with the conformational change in solution allow for determining if sulfonylureas should have high or low inhibition activity. QM/MM calculations were also carried out in order to identify the role of the amino acid residues and the effects involved in the stabilization of the active conformation in the binding pocket. On the other hand, the analysis of the frontier molecular orbitals of the sulfonylureas in the binding pocket allowed us to explain the inhibitory activity in terms of the reactivity of the carbonyl carbon.

Idioma originalEnglish
Páginas (desde-hasta)926-932
Número de páginas7
PublicaciónJournal of Chemical Information and Modeling
Volumen54
N.º3
DOI
EstadoPublished - 24 mar 2014

Huella dactilar

Gibbs free energy
Conformations
Theoretical Models
Molecular orbitals
energy
Amino acids
Carbon
Stabilization
Gases
Chemical activation
stabilization
Amino Acids
activation

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)
  • Computer Science Applications
  • Library and Information Sciences
  • Medicine(all)

Citar esto

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abstract = "The inhibitory activity of 15 sulfonylureas on acetohydroxyacid synthase (AHAS) is addressed theoretically in order to stress how important the conformation is to explain their differences as AHAS inhibitors. The study includes calculations in gas phase, solution, and in the enzymatic environment. The results suggest that both the activation Gibbs free energy and Gibbs free energy change associated with the conformational change in solution allow for determining if sulfonylureas should have high or low inhibition activity. QM/MM calculations were also carried out in order to identify the role of the amino acid residues and the effects involved in the stabilization of the active conformation in the binding pocket. On the other hand, the analysis of the frontier molecular orbitals of the sulfonylureas in the binding pocket allowed us to explain the inhibitory activity in terms of the reactivity of the carbonyl carbon.",
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How important is the synclinal conformation of sulfonylureas to explain the inhibition of AHAS : A theoretical study. / Jaña, Gonzalo A.; Delgado, Eduardo J.; Medina, Fabiola E.

En: Journal of Chemical Information and Modeling, Vol. 54, N.º 3, 24.03.2014, p. 926-932.

Resultado de la investigación: Article

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AB - The inhibitory activity of 15 sulfonylureas on acetohydroxyacid synthase (AHAS) is addressed theoretically in order to stress how important the conformation is to explain their differences as AHAS inhibitors. The study includes calculations in gas phase, solution, and in the enzymatic environment. The results suggest that both the activation Gibbs free energy and Gibbs free energy change associated with the conformational change in solution allow for determining if sulfonylureas should have high or low inhibition activity. QM/MM calculations were also carried out in order to identify the role of the amino acid residues and the effects involved in the stabilization of the active conformation in the binding pocket. On the other hand, the analysis of the frontier molecular orbitals of the sulfonylureas in the binding pocket allowed us to explain the inhibitory activity in terms of the reactivity of the carbonyl carbon.

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