Structural insight into the glucokinase-ligands interactions. Molecular docking study |
| |
| Institution: | 1. Université de Toulouse, INSA, UPS, INP, LISBP, 135 Avenue de Rangueil, F-31077 Toulouse, France;2. INRA, UMR792 Ingénierie des Systèmes Biologiques et des Procédés, F-31400 Toulouse, France;3. CNRS, UMR5504, 135 Avenue de Rangueil, F-31400 Toulouse, France;4. Université Pierre-et-Marie-Curie, 4 Place Jussieu, 75005 Paris, France;5. INSERM U773, Faculté de Médecine Bichat-Beaujon, 75018 Paris, France;6. Solvay, Product Compliance, 52 rue de la Haie-Coq, 93306 Aubervilliers, France;1. State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, PR China;2. Technology Development, Daqing Oilfield Company Limited, Daqing 163000, PR China;3. Research Institute of Exploration and Development of Daqing Oilfield Company Ltd., Daqing 163000, PR China;4. Key Laboratory of Tobacco Flavor Basic Research of CNTC, Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou 450000, PR China |
| |
| Abstract: | Glucokinase (GK) plays a key role in the regulation of hepatic glucose metabolism. Inactivation of GK is associated with diabetes, and an increase of its activity is linked to hypoglycemia. Possibility to regulate the GK activity using small chemical compounds as allosteric activators induces the scientific interest to the study of the activation mechanism and to the development of new allosteric glucokinase activators.Interaction of glucokinase with ligands is the first step of the complicated mechanism of regulation of the GK functioning. In this paper, we study the interaction of GK with native (glucose) and synthetic (allosteric activators) ligands using molecular docking method. Calculations demonstrate the ability of molecular docking programs to accurately reproduce crystallized ligand poses and conformations and to calculate a free energy of binding with satisfactory accuracy. Correlation between the free energy of binding and the bioactivity of activators is discussed. These results provide a new insight into protein–ligand interactions and can be used for the engineering of new activators. |
| |
| Keywords: | Glucokinase Activators Docking Interaction energy AutoDock Vina |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
