In silico and kinetic modelling of new allosteric inhibitor for human protease ADAM17


Congratulations to Marian Bienstein on his recent publication!

Revealing the ADAM17 inhibition mechanisms to give methodology for studying selective inhibition towards the design of pharmaceutical substances with higher selectivity

In Marian's new publication, allosteric inhibition of the human endogenous protease ADAM17 was investigated. A newly found compound (CID17) was previously shown to be an active modulator capable of allosterically regulating the activity of ADAM17. Experimental kinetic modeling as well as computational molecular docking experiments proved the previously hypothesized modulatory inhibitor mechanism. Molecular docking identified the exact binding site of the described exosite inhibitor. Furthermore, the docking results and characterization of the inhibitor serve as a basis for future development of new allosteric inhibitors for ADAM17 in a high-throughput procedure. Thus, the inhibitor found could replace the inhibitors currently used in medicine, which are currently responsible for severe side effects due to their non-specific inhibition of metalloproteases.

This work was performed in the Computational Biology division and was made possible by RWTH Aachen University (ERS Seed Fund Call MScale) and DFG grant DR1013/1 1. The simulations were performed using computational resources provided by JARA-HPC at RWTH Aachen University as part of project RWTH0116.

To learn more, please access the full paper on Publications and patents and

Bienstein M., Minond D., Schwaneberg U., Davari M.D., Yildiz D.; In Silico and Experimental ADAM17 Kinetic Modeling as Basis for Future Screening System for Modulators; IJMS, 2022, DOI:10.3390/ijms23031368

  Graphical illustration of ADAM17. Copyright: © International Journal of Molecular Science, MDPI Graphical illustration of ADAM17.