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 original | English |
|---|---|
| Páginas (desde-hasta) | 926-932 |
| Número de páginas | 7 |
| Publicación | Journal of Chemical Information and Modeling |
| Volumen | 54 |
| N.º | 3 |
| DOI | |
| Estado | Published - 24 mar 2014 |
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ASJC Scopus subject areas
- Chemistry(all)
- Chemical Engineering(all)
- Computer Science Applications
- Library and Information Sciences
- Medicine(all)
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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
TY - JOUR
T1 - How important is the synclinal conformation of sulfonylureas to explain the inhibition of AHAS
T2 - A theoretical study
AU - Jaña, Gonzalo A.
AU - Delgado, Eduardo J.
AU - Medina, Fabiola E.
PY - 2014/3/24
Y1 - 2014/3/24
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84897008464&partnerID=8YFLogxK
U2 - 10.1021/ci400721y
DO - 10.1021/ci400721y
M3 - Article
C2 - 24548139
AN - SCOPUS:84897008464
VL - 54
SP - 926
EP - 932
JO - Journal of Chemical Information and Modeling
JF - Journal of Chemical Information and Modeling
SN - 1549-9596
IS - 3
ER -