Akademik Veri Yönetim Sistemi
4th Eurasia Biochemical Approaches & Technologies (EBAT) 2022, Antalya, Türkiye, 3 - 06 Kasım 2022, ss.268
Hyperactive Hsp90, which is overexpressed in cancer cells and causes accumulation of oncogenicrelated proteins that impair cellular homeostasis, has emerged as a therapeutic cancer target with
degradation of associated proteins induced by Hsp90 inhibition.
1
In addition, Hsp90 inhibitors have a
wide therapeutic window for cancer treatment, as the level of Hsp90 is distinctive between cancer
cells and normal cells. Overexpression of Hsp90 causes dysregulation of chaperone functions and
destroys cellular homeostasis, resulting in cell cycle acceleration, endless proliferation, and decreased
sensitivity to anti-growth signals that are characteristic of tumors.
2,3
In this study, a virtual screening
method was used to identify novel inhibitors of Hsp90 with these effects in mind.
In virtual screening, Hsp90 structure (PDB: 4W7T) was chosen as the receptor, all drugs in the Drugbank
database (~10767) were downloaded and were used as ligand. SP/XP hierarchical virtual screening
were performed to identify inhibitors targeting the Hsp90 protein in the screening process. Clusters
were created for drugs determined by screening using the Maestro Canvas Similarity and Clustering
program. These values were examined and hit molecules were determined. After, molecular dynamics
simulation studies (200 ns) were performed to analyze the dynamics between Hsp90-drug complexes.
System stabilities of the complexes was determined with RMSD and RMSF graphs and it was predicted
that they could be new Hsp90 inhibitors. In addition, this study can be supported by in vitro studies
and may lead to the design of potential new inhibitors.