Molecular dynamics simulation of the interaction between protein tyrosine phosphatase 1B and aryl diketoacid derivatives

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.

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► Monomeric and dimeric aryl diketoacids adopt different bonding modes.
► The van der Waals interaction plays an important role.
► The van der Waals interaction energy and their IC50 values are closely correlated.
► The van der Waals and the hydrogen bond interaction are mutually cooperative.