title: Molecular dynamics simulation of the interaction between protein tyrosine phosphatase 1B and aryl diketoacid derivatives.
abstract: The protein tyrosine phosphatase 1B (PTP-1B) is acknowledged as an outstanding therapeutic target for the treatment of diabetes, obesity and cancer. In this work, six aryl diketoacid compounds have been studied on the basis of molecular dynamics simulations. Hydrogen bonds, binding energies and conformation changes of the WPD loop have been analyzed. The results indicated that their activation model falls into two parts: the target region of the monomeric aryl diketoacid compounds is the active site, whereas the target region of the dimeric aryl diketoacid compounds is the WPD loop or the R loop. The van der Waals interactions exhibit stronger effects than the short-range electrostatic interactions. The van der Waals interaction energy and the IC50 values exhibit an approximately exponential relationship. Furthermore, the van der Waals interactions cooperate with the hydrogen bond interactions. This study provides a more thorough understanding of the PTP-1B inhibitor binding processes.
authors.affiliation: Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, Institute of Theoretical Chemistry, School of Chemistry & Chemical Engineering, Shandong University, Jinan 250100, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Liu
authors.forename: Chengbu
authors.initials: C
authors.lastname: Liu
mesh_terms: D019440:Anti-Obesity Agents / Q000737:chemistry*; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D007651:Keto Acids / Q000737:chemistry*; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D019440:Anti-Obesity Agents; D004791:Enzyme Inhibitors; D007651:Keto Acids; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1