Predicted configuration and stability of the ALKBH5/USP36 complex

Abstract

Abstract Background Alpha-ketoglutarate dependent dioxygenase-5 (ALKBH5), a de-ubiquinating enzyme, is abnormally activated and plays important functions in glioblastoma formation. Ubiquitin-specific peptidase 36 (USP36) is crucial for maintaining ALKBH5 stability and controlling ALKBH5-mediated gene expression in glioblastoma stem cells. Reduced cell proliferation, worsened self-renewal, and increased sensitivity to temozolomide (TMZ) therapy were all effects of USP36 depletion. Elucidation of the ADAT2/USP36 complex structure may therefore facilitate the development of drugs that can block complex formation. Methods We have used the ClusPro web server for protein-protein docking to visualize and analyze the complex and GROMACS to perform molecular dynamics simulation. Results ClusPro protein docking analysis demonstrates the loose peripheral position of ADAT2 in the ADAT2/USP36 complex. Molecular dynamics simulation of ALKBH5 docked to USP36 suggests that ALKBH5/USP36 is not a stable structure. Conclusion The results of protein-protein docking and molecular dynamics simulation imply that the ADAT2/USP36 complex is not stable and might be disrupted by a therapeutic molecule or molecules, improving the prognosis of glioblastoma. Knowledge of the ADAT2/USP36 complex structure may facilitate the development of drugs that can block or disrupt complex formation.