Biomedical Chemistry: Research and Methods, 2018, 1(1), e00008

Investigation in silico the interaction of oxazolinyl derivatives of [17(20)E]-21-norpregnene with androgen receptor.

K.A. Shcherbakov1*, D.S. Shcherbinin2, V.A. Kostin1, V.A. Zolottsev1, A.Yu. Misharin1, A.V. Veselovsky3

1Institute of Biomedical Chemistry, 10 Pogodinskaya str., Moscow 119121, Russia, *e-mail: kirill.soff@gmail.com
2Center for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, Moscow, Russia
3Institute of Physiologically Active Compounds, Moscow region, Chernogolovka, Russia

Keywords: : prostate cancer, androgen receptor, derivatives of pregna-5,17(20)-diene, docking, molecular dynamics, MM-GBSA method

DOI: 10.18097/BMCRM00008

The whole version of this paper is available in Russian.

The ability of novel oxazolinyl derivatives of pregna-5,17(20)-diene to interact with the androgen receptor (AR) was investigated using molecular modelling methods. Six new derivatives differed in oxazolinyl radicals in 17 position were used. It was shown that all compounds were able to docked in the ligand-binding domain of AR only when the AR helix-12 was removed. It is suggested that these compounds have antagonistic properties. Results of docking and simulation of molecular dynamics with estimation of binding energy allow to predict that two compounds can be effective AR antagonists.

Figure 1. Oxazolinyl derivatives of of pregna-5,17(20)-diene used in the study.
Figure 2. Overlaped structures 2 (magenta sticks) and EM-5744 (cyan sticks) in the AR binding site.
Figure 3. 2D diagram of compound 2 interaction with AR. Red semicircles represent residues interacting by hydrophobic force; green dotted line shows H-bond
Figure 4. RMSD of AR complexes with compounds 1-6 during simulation of molecular dynamics. A – RMSD for protein; B – RMSD for ligands.

CLOSE
Table 1. Average values of H-bonds and values of binding energy of ligands 1-6 with AR

ACKNOWLEDGEMENTS

This study was supported by Russian State Academies of Sciences Fundamental Research Program for 2013–2020.

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