Computational Insight into Protein Tyrosine Phosphatase 1B Inhibition: A Case Study of the Combined Ligand- and Structure-Based Approach.

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is an attractive target for treating cancer, obesity, and type 2 diabetes. In our work, the way of combined ligand- and structure-based approach was applied to analyze the characteristics of PTP1B enzyme and its interaction with competitive inhibitors. Firstly, the pharmacophore model of PTP1B inhibitors was built based on the common feature of sixteen compounds. It was found that the pharmacophore model consisted of five chemical features: one aromatic ring (R) region, two hydrophobic (H) groups, and two hydrogen bond acceptors (A). To further elucidate the binding modes of these inhibitors with PTP1B active sites, four docking programs (AutoDock 4.0, AutoDock Vina 1.0, standard precision (SP) Glide 9.7, and extra precision (XP) Glide 9.7) were used. The characteristics of the active sites were then described by the conformations of the docking results. In conclusion, a combination of various pharmacophore features and the integration information of structure activity relationship (SAR) can be used to design novel potent PTP1B inhibitors.

• Authors: Xiangyu Zhang, Hailun Jiang, Wei Li, Jian Wang, Maosheng Cheng
• Journal: Computational and mathematical methods in medicine (Comput Math Methods Med) Vol. 2017 Pg. 4245613 ( 2017) ISSN: 1748-6718 [Electronic] United States
• PMID: 29441120 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Ligands
• Proteins
• PTPN1 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 1

Topics

• Algorithms
• Binding Sites
• Binding, Competitive
• Catalytic Domain
• Diabetes Mellitus, Type 2 (metabolism)
• Diagnosis, Computer-Assisted
• Enzyme Inhibitors (chemistry)
• Humans
• Hydrogen Bonding
• Inhibitory Concentration 50
• Ligands
• Molecular Docking Simulation
• Protein Binding
• Protein Conformation
• Protein Tyrosine Phosphatase, Non-Receptor Type 1 (antagonists & inhibitors)
• Proteins (chemistry)
• Software
• Structure-Activity Relationship