1st International Conference on Chemo and BioInformatics, ICCBIKG 2021, (403-406)
AUTHOR(S) / АУТОР(И): Suzana S. Jovanović-Šanta, Esma Isenović, Julijana A. Petrović, Yaraslau U. Dzichenka
E-ADRESS / Е-АДРЕСА: suzana.jovanovic-santa@dh.uns.ac.rs, isenovic@yahoo.com, dichenko@iboch.by
DOI: 10.46793/ICCBI21.403JS
ABSTRACT / САЖЕТАК:
About 75% of breast cancers express estrogen receptors (ERs), which is a good base for an efficient endocrine therapy. This gives the opportunity for the treatment of patients with antiestrogens, compounds that bind to the ERs and thus compete to estradiol (E2), preventing its action in progression of estrogen-depending cancers.
Here we present results of testing the effect of the modified steroids, namely 17-substituted 16-nitrile 16,17-secoestrane compounds on the E2-ER complex forming, its stability, nuclear translocation and binding to DNA. Almost all compounds in moderate to high rate induced lower forming of this complex, destabilizing it – they increased Kd of this complex and decreased number of binding sites. Complex formed in the presence of some test secosteroids could pass to the nucleus, while other compounds inhibited translocation. In the presence of some compounds binding of the formed complex E2-ER to DNA was noticed.
Docking followed molecular dynamics simulation was performed to reveal binding mode of E2 to ER in the presence of test secosteroids. Amino acids important for binding process and complex stabilization were detected. Analysis of the simulation data allowed identifying key amino acids and type of binding of the secoestrane compounds, important for high affinity binding of the steroidal compounds.
KEY WORDS / КЉУЧНЕ РЕЧИ:
ER, secoestrane compounds, docking, molecular dynamics
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