We present a combined computational and experimental study of the interaction of the Box A of the HMGB1 protein and carbenoxolone, an inhibitor of its pro-inflammatory activity. The computational approach consists of classical molecular dynamics (MD) simulations based on the GROMOS force field with quantum-refined (QRFF) atomic charges for the ligand. Experimental data consist of fluorescence intensities, chemical shift displacements, saturation transfer differences and intermolecular Nuclear Overhauser Enhancement signals. Good agreement is found between observations and the conformation of the ligand-protein complex resulting from QRFF-MD. In contrast, simple docking procedures and MD based on the unrefined force field provide models inconsistent with experiment. The ligand-protein binding is dominated by non-directional interactions.
The binding domain of the HMGB1 inhibitor carbenoxolone: Theory and experiment / L. Mollica, A. Curioni, W. Andreoni, M.E. Bianchi, G. Musco. - In: CHEMICAL PHYSICS LETTERS. - ISSN 0009-2614. - 456:4-6(2008), pp. 236-242. [10.1016/j.cplett.2008.03.022]
The binding domain of the HMGB1 inhibitor carbenoxolone: Theory and experiment
L. MollicaPrimo
;A. CurioniSecondo
;M.E. BianchiPenultimo
;
2008
Abstract
We present a combined computational and experimental study of the interaction of the Box A of the HMGB1 protein and carbenoxolone, an inhibitor of its pro-inflammatory activity. The computational approach consists of classical molecular dynamics (MD) simulations based on the GROMOS force field with quantum-refined (QRFF) atomic charges for the ligand. Experimental data consist of fluorescence intensities, chemical shift displacements, saturation transfer differences and intermolecular Nuclear Overhauser Enhancement signals. Good agreement is found between observations and the conformation of the ligand-protein complex resulting from QRFF-MD. In contrast, simple docking procedures and MD based on the unrefined force field provide models inconsistent with experiment. The ligand-protein binding is dominated by non-directional interactions.File | Dimensione | Formato | |
---|---|---|---|
1-s2.0-S0009261408003345-main.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
1.52 MB
Formato
Adobe PDF
|
1.52 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.