38 research outputs found
ΠΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΠ΅ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΡ ΠΏΡΠΎΡΠ΅Π°Π·Ρ 3Π‘Lpro Π²ΠΈΡΡΡΠ° COVID-19: ΡΠ΅ΠΏΠΎΠ·ΠΈΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π»Π΅ΠΊΠ°ΡΡΡΠ²
Pneumonia caused by the COVID-19 virus has led to quick search of drugs that would able to block the spread of this virus. A standard way of drug development is a long process. One approach that can significantly accelerate drug development is drug reposition. In this study a virtual screening of the database of approved drugs has been used for search inhibitors against 3Π‘Lpro COVID-19, the main protease of COVID-19. Molecular docking, simulation of molecular dynamics and binding energy estimation by MM-GBSA method allowed to select several compounds for further experimental testing. The most promising drugs are the HIV protease inhibitor Indinavir, the inhibitor of protease hepatitis C Telaprevir, the antiulcer drug Dalargin, and the ErB receptor tyrosine kinase inhibitor NeratinibΠΡΠΏΡΡΠΊΠ° Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ, Π²ΡΠ·Π²Π°Π½Π½Π°Ρ Π²ΠΈΡΡΡΠΎΠΌ COVID-19, ΡΡΠΈΠΌΡΠ»ΠΈΡΠΎΠ²Π°Π»Π° ΠΏΠΎΠΈΡΠΊ ΡΡΠ΅Π΄ΡΡΠ², ΡΠΏΠΎΡΠΎΠ±Π½ΡΡ
Π±Π»ΠΎΠΊΠΈΡΠΎΠ²Π°ΡΡ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½ΠΈΠ΅ ΡΡΠΎΠ³ΠΎ Π²ΠΈΡΡΡΠ°. Π‘ΡΠ°Π½Π΄Π°ΡΡΠ½Π°Ρ ΡΡ
Π΅ΠΌΠ° ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ Π½ΠΎΠ²ΡΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ² ΡΠ²Π»ΡΠ΅ΡΡΡ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΡΠΌ ΠΏΡΠΎΡΠ΅ΡΡΠΎΠΌ. ΠΠ΄Π½ΠΈΠΌ ΠΈΠ· ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΎΠ², ΠΊΠΎΡΠΎΡΡΠ΅ ΠΌΠΎΠ³ΡΡ ΡΠ΅Π·ΠΊΠΎ ΡΡΠΊΠΎΡΠΈΡΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΡ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ², ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ΅ΠΏΠΎΠ·ΠΈΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π»Π΅ΠΊΠ°ΡΡΡΠ² (Ρ.Π΅. ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΆΠ΅ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² ΠΏΠΎ Π½ΠΎΠ²ΡΠΌ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΈΡΠΌ). Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ Π²ΠΈΡΡΡΠ°Π»ΡΠ½ΡΠΉ ΡΠΊΡΠΈΠ½ΠΈΠ½Π³ Π²Π΅ΡΠ΅ΡΡΠ², ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ
ΡΡ Π² Π±Π°Π·Π΅ ΡΠ°Π·ΡΠ΅ΡΠ΅Π½Π½ΡΡ
ΠΊ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ Π»Π΅ΠΊΠ°ΡΡΡΠ², ΠΏΡΠΎΡΠΈΠ² ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΉ ΠΏΡΠΎΡΠ΅Π°Π·Ρ COVID-19 β 3Π‘Lpro. ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠΉ Π΄ΠΎΠΊΠΈΠ½Π³, ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠΉ Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠΈ ΠΈ ΠΎΡΠ΅Π½ΠΊΠ° ΡΠ½Π΅ΡΠ³ΠΈΠΈ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ MM-GBSA ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ»ΠΈ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠΈΡΡ ΡΡΠ΄ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Π΄Π»Ρ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠ΅Π³ΠΎ ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ. ΠΠ°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΡΠΌΠΈ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π°ΠΌΠΈ Π² ΡΡΠΎΠΌ ΠΏΠ»Π°Π½Π΅ ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡ ΠΏΡΠΎΡΠ΅Π°Π·Ρ ΠΠΠ§ Indinavir, ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡ ΠΏΡΠΎΡΠ΅Π°Π·Ρ Π³Π΅ΠΏΠ°ΡΠΈΡΠ° Π‘ Telaprevir, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΡΠΎΡΠΈΠ²ΠΎΡΠ·Π²Π΅Π½Π½ΡΠΉ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ Dalargin ΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡ ΡΠΈΡΠΎΠ·ΠΈΠ½ΠΊΠΈΠ½Π°Π·Ρ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ErB Neratinib
ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΠ°Π½Π°Π»ΡΠ½ΡΡ Π±Π»ΠΎΠΊΠ°ΡΠΎΡΠΎΠ² NMDA ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° Π² ΡΡΠ΄Ρ ΠΊΠΎΠ½ΡΡΠ³Π°ΡΠΎΠ² ΠΌΠ΅ΡΠΈΠ»Π΅Π½ΠΎΠ²ΠΎΠ³ΠΎ ΡΠΈΠ½Π΅Π³ΠΎ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ QSAR ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠ³ΠΎ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ
29 conjugates of methylene blue and four chemical structures, including derivatives of carbazole, tetrahydrocarbazole, substituted indoles and Ξ³-carboline, combined with a 1-oxopropylene spacer have been studied as channel blockers of the NMDA receptor (binding site of MK-801) by using four QSAR methods (multiple linear regression, random forest, support vector machine, Gaussian process) and molecular docking. QSAR models have satisfactory characteristics. The analysis of regression models at the statistical level revealed an important role of the hydrogen bond in the complex formation. This was also confirmed by the study of modeled by docking complexes. It was found that the increase in the inhibitory activity of the part of compounds could be attributed to appearance of additional H bonds between the ligands and the receptor.Π‘ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ 4-Ρ
ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² QSAR (ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²Π΅Π½Π½Π°Ρ Π»ΠΈΠ½Π΅ΠΉΠ½Π°Ρ ΡΠ΅Π³ΡΠ΅ΡΡΠΈΡ, ΡΠ»ΡΡΠ°ΠΉΠ½ΡΠΉ Π»Π΅Ρ, ΠΌΠ΅ΡΠΎΠ΄ ΠΎΠΏΠΎΡΠ½ΡΡ
Π²Π΅ΠΊΡΠΎΡΠΎΠ², Π³Π°ΡΡΡΠΎΠ²ΡΠΊΠΈΠΉ ΠΏΡΠΎΡΠ΅ΡΡ) ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠ³ΠΎ Π΄ΠΎΠΊΠΈΠ½Π³Π° ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Ρ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ Π±Π»ΠΎΠΊΠ°ΡΠΎΡΠΎΠ² NMDA ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° (ΡΠ°ΠΉΡ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ ΠΠ-801) 29 ΠΊΠΎΠ½ΡΡΠ³Π°ΡΠΎΠ² ΠΌΠ΅ΡΠΈΠ»Π΅Π½ΠΎΠ²ΠΎΠ³ΠΎ ΡΠΈΠ½Π΅Π³ΠΎ ΠΈ ΡΠ΅ΡΡΡΠ΅Ρ
ΡΠΈΠΏΠΎΠ² ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ, Π²ΠΊΠ»ΡΡΠ°Ρ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΠ΅ ΠΊΠ°ΡΠ±Π°Π·ΠΎΠ»Π°, ΡΠ΅ΡΡΠ°Π³ΠΈΠ΄ΡΠΎΠΊΠ°ΡΠ±Π°Π·ΠΎΠ»Π°, Π·Π°ΠΌΠ΅ΡΠ΅Π½Π½ΡΡ
ΠΈΠ½Π΄ΠΎΠ»ΠΎΠ² ΠΈ Ξ³-ΠΊΠ°ΡΠ±ΠΎΠ»ΠΈΠ½Π°, ΠΎΠ±ΡΠ΅Π΄ΠΈΠ½Π΅Π½Π½ΡΡ
1-ΠΎΠΊΡΠΎΠΏΡΠΎΠΏΠΈΠ»Π΅Π½ΠΎΠ²ΡΠΌ ΡΠΏΠ΅ΠΉΡΠ΅ΡΠΎΠΌ. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ QSAR ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΈΠΌΠ΅ΡΡ ΡΠ΄ΠΎΠ²Π»Π΅ΡΠ²ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΡΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠΈ. ΠΠ° ΠΎΡΠ½ΠΎΠ²Π΅ Π°Π½Π°Π»ΠΈΠ·Π° ΡΠ΅Π³ΡΠ΅ΡΡΠΈΠΎΠ½Π½ΡΡ
ΠΌΠΎΠ΄Π΅Π»Π΅ΠΉ Π½Π° ΡΡΠ°ΡΠΈΡΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΡΡΠΎΠ²Π½Π΅ Π²ΡΡΠ²Π»Π΅Π½Π° Π²Π°ΠΆΠ½Π°Ρ ΡΠΎΠ»Ρ Π²ΠΎΠ΄ΠΎΡΠΎΠ΄Π½ΠΎΠΉ ΡΠ²ΡΠ·ΠΈ ΠΏΡΠΈ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΠΈ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ°. ΠΡΠΎ Π½Π°ΡΠ»ΠΎ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π΅Π½ΠΈΠ΅ ΠΏΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΈ ΠΌΠΎΠ΄Π΅Π»Π΅ΠΉ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ², ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠΌ Π΄ΠΎΠΊΠΈΠ½Π³ΠΎΠΌ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΡΡΡΠ΅ΠΉ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΡΠ°ΡΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½ΠΎ ΠΏΠΎΡΠ²Π»Π΅Π½ΠΈΠ΅ΠΌ Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΡΡ
Π-ΡΠ²ΡΠ·Π΅ΠΉ ΠΌΠ΅ΠΆΠ΄Ρ Π»ΠΈΠ³Π°Π½Π΄Π°ΠΌΠΈ ΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠΌ
ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ in silico Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ 2β-{[(e)-Π°Π½Π΄ΡΠΎΡΡ-5-Π΅Π½-17-ΠΈΠ»ΠΈΠ΄Π΅Π½]-ΠΌΠ΅ΡΠΈΠ»}ΠΎΠΊΡΠ°Π·ΠΎΠ»ΠΈΠ½ΠΎΠ² Ρ Π°Π½Π΄ΡΠΎΠ³Π΅Π½ΠΎΠ²ΡΠΌ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠΌ
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.ΠΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠ³ΠΎ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΎΡΠ΅Π½Π΅Π½Π° ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ Π½ΠΎΠ²ΡΡ
Π°Π·ΠΎΡΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ
ΡΡΠ΅ΡΠΎΠΈΠ΄Π½ΡΡ
ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ
2β-{[(E)-Π°Π½Π΄ΡΠΎΡΡ-5-Π΅Π½-17-ΠΈΠ»ΠΈΠ΄Π΅Π½]-ΠΌΠ΅ΡΠΈΠ»}ΠΎΠΊΡΠ°Π·ΠΎΠ»ΠΈΠ½ΠΎΠ² Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΎΠ²Π°ΡΡ Ρ Π°Π½Π΄ΡΠΎΠ³Π΅Π½Π½ΡΠΌ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠΌ. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Ρ 6 ΠΎΠΊΡΠ°Π·ΠΎΠ»ΠΈΠ½ΠΎΠ²ΡΡ
ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ
17(20)Π-ΠΏΡΠ΅Π³Π½Π°-5,17(20)-Π΄ΠΈΠ΅Π½Π°, ΡΠ°Π·Π»ΠΈΡΠ°ΡΡΠΈΡ
ΡΡ ΡΡΡΡΠΊΡΡΡΠΎΠΉ Π³Π΅ΡΠ΅ΡΠΎΡΠΈΠΊΠ»Π°. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π²ΡΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΡΠΏΠΎΡΠΎΠ±Π½Ρ ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΡΡ Ρ Π°Π½Π΄ΡΠΎΠ³Π΅Π½Π½ΡΠΌ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠΌ ΡΠΎΠ»ΡΠΊΠΎ Π² ΡΠ»ΡΡΠ°Π΅, ΠΊΠΎΠ³Π΄Π° ΠΈΠ· ΡΡΡΡΠΊΡΡΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° Π±ΡΠ»Π° ΡΠ΄Π°Π»Π΅Π½Π° 12 ΡΠΏΠΈΡΠ°Π»Ρ. ΠΡΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°ΡΡ, ΡΡΠΎ Π΄Π°Π½Π½ΡΠ΅ Π»ΠΈΠ³Π°Π½Π΄Ρ Π΄ΠΎΠ»ΠΆΠ½Ρ ΠΏΡΠΎΡΠ²Π»ΡΡΡ Π°Π½ΡΠ°Π³ΠΎΠ½ΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π°. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ Π΄ΠΎΠΊΠΈΠ½Π³Π° ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠΉ Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠΈ Ρ ΠΎΡΠ΅Π½ΠΊΠΎΠΉ ΡΠ½Π΅ΡΠ³ΠΈΠΈ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ»ΠΈ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ, ΡΡΠΎ Π΄Π²Π° ΠΈΠ· ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠΌΠΈ Π°Π½ΡΠ°Π³ΠΎΠ½ΠΈΡΡΠ°ΠΌΠΈ Π°Π½Π΄ΡΠΎΠ³Π΅Π½Π½ΠΎΠ³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°
Π€ΠΈΠ·ΠΈΠΊΠΎ-Ρ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ²Π° ΠΌΡΡΠ°Π½ΡΠ½ΡΡ ΡΠΎΡΠΌ L-Π°ΡΠΏΠ°ΡΠ°Π³ΠΈΠ½Π°Π·Ρ ΠΈΠ· Rhodospirillum rubrum, ΠΎΠ±Π»Π°Π΄Π°ΡΡΠΈΡ Π°Π½ΡΠΈΡΠ΅Π»ΠΎΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ
Rru_A3730 protein is a bacterial Rhodospirillum rubrum L-asparaginase (RrA), which is known by its anticancer activity. RrA variants with point amino acid substitutions in the region of 150 amino acids residues: RrA17N, K149E, RrAE149R, V150P, F151T, RrΠ17N, E149R, V150P, RrAE149R, V150P, showed antiproliferative properties, and also by their ability to suppress telomerase activity. This work is devoted to comparison of physical-chemical and catalytic properties of these mutant forms of RrA. It is shown that pH optimum is in the alkaline zone (8.5 β 9.3); L-glutaminase and D-asparaginase activity is respectively not more than 0.1% and 1.6% of L-asparaginase for all studied variants of RrA. The presence of the N17-terminal amino acid sequence MASMTGGQMGRGSSRQ of the capsid protein of bacteriophage T7 in the RrA structure leads to an increase in the thermal stability of mutant RrA analogues (from 50Β°C to 56Β°C) and their resistance to denaturation in the presence of 3 β 4 M urea. It is of Metal ions exhibit multidirectional effects on L-asparaginase activity of RrA. K+, Ca2+, Zn2+, Cs+, Co2+ in significantly affect the activity of L-asparaginase, while Mn2+, Cu2+, Fe3+ ions inhibit it. There was no correlation between antitelomerase (antiproliferative) activity and kinetic properties of mutant forms of L-asparaginase RrA.ΠΠ΅Π»ΠΎΠΊ Rru_A3730, ΠΈΠ·Π²Π΅ΡΡΠ½ΡΠΉ ΠΊΠ°ΠΊ Π±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½Π°Ρ L-Π°ΡΠΏΠ°ΡΠ°Π³ΠΈΠ½Π°Π·Π° Rhodospirillum rubrum, ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅Ρ ΠΈΠ½ΡΠ΅ΡΠ΅Ρ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ ΡΡΠ΅Π΄ΡΡΠ²Π°, ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎ Π΅Ρ Π²Π°ΡΠΈΠ°Π½ΡΡ Ρ ΡΠΎΡΠ΅ΡΠ½ΡΠΌΠΈ Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡΠ½ΡΠΌΠΈ Π·Π°ΠΌΠ΅Π½Π°ΠΌΠΈ Π² ΡΠ°ΠΉΠΎΠ½Π΅ 150 Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡΠ½ΠΎΠ³ΠΎ ΠΎΡΡΠ°ΡΠΊΠ° (Π°.ΠΊ.ΠΎ.): RrA17N, K149E, RrAE149R, V150P, F151T, RrΠ17N, E149R, V150P, RrAE149R, V150P, ΠΎΠ±Π»Π°Π΄Π°ΡΡΠΈΠ΅ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ Π°Π½ΡΠΈΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΡΠΌΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ, Π½ΠΎ ΠΈ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡΡ ΠΏΠΎΠ΄Π°Π²Π»ΡΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠ΅Π»ΠΎΠΌΠ΅ΡΠ°Π·Ρ. ΠΠ°Π½Π½Π°Ρ ΡΠ°Π±ΠΎΡΠ° ΠΏΠΎΡΠ²ΡΡΠ΅Π½Π° ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ ΡΠΈΠ·ΠΈΠΊΠΎ-Ρ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈ ΠΊΠ°ΡΠ°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ²ΠΎΠΉΡΡΠ² ΡΡΠΈΡ
ΠΌΡΡΠ°Π½ΡΠ½ΡΡ
ΡΠΎΡΠΌ RrA. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π΄Π»Ρ Π²ΡΠ΅Ρ
ΠΈΠ·ΡΡΠ΅Π½Π½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² RrA ΡΠ ΠΎΠΏΡΠΈΠΌΡΠΌ Π½Π°Ρ
ΠΎΠ΄ΠΈΡΡΡ Π² ΡΠ΅Π»ΠΎΡΠ½ΠΎΠΉ Π·ΠΎΠ½Π΅ (8.5 β 9.3); L-Π³Π»ΡΡΠ°ΠΌΠΈΠ½Π°Π·Π½Π°Ρ ΠΈ D-Π°ΡΠΏΠ°ΡΠ°Π³ΠΈΠ½Π°Π·Π½Π°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠΎΡΡΠ°Π²Π»ΡΡΡ, ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ, Π½Π΅ Π±ΠΎΠ»Π΅Π΅ 0.1% ΠΈ 1.6% ΠΎΡ L-Π°ΡΠΏΠ°ΡΠ°Π³ΠΈΠ½Π°Π·Π½ΠΎΠΉ. ΠΡΠΈΡΡΡΡΡΠ²ΠΈΠ΅ 17N-ΠΊΠΎΠ½ΡΠ΅Π²ΠΎΠΉ Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡΠ½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ MASMTGGQQMGRGSSRQ ΠΊΠ°ΠΏΡΠΈΠ΄Π½ΠΎΠ³ΠΎ Π±Π΅Π»ΠΊΠ° Π±Π°ΠΊΡΠ΅ΡΠΈΠΎΡΠ°Π³Π° Π’7 Π² ΡΡΡΡΠΊΡΡΡΠ΅ RrA ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΡΠ΅ΡΠΌΠΎΡΡΠ°Π±ΠΈΠ»ΡΠ½ΠΎΡΡΠΈ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ
Π°Π½Π°Π»ΠΎΠ³ΠΎΠ² RrA (ΠΎΡ 50Β°Π‘ Π΄ΠΎ 56Β°Π‘) ΠΈ ΠΈΡ
ΡΡΡΠΎΠΉΡΠΈΠ²ΠΎΡΡΠΈ ΠΊ Π΄Π΅Π½Π°ΡΡΡΠ°ΡΠΈΠΈ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ 3 β 4 Π ΠΌΠΎΡΠ΅Π²ΠΈΠ½Ρ. ΠΡΡΠ²Π»Π΅Π½ ΡΠ°Π·Π½ΠΎΠ½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΡΠΉ ΡΡΡΠ΅ΠΊΡ ΠΈΠΎΠ½ΠΎΠ² ΠΌΠ΅ΡΠ°Π»Π»ΠΎΠ² Π½Π° L-Π°ΡΠΏΠ°ΡΠ°Π³ΠΈΠ½Π°Π·Π½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² RrA: ΠΈΠΎΠ½Ρ K+, Ca2+, Zn2+, Cs+, Co2+ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ Π½Π΅ Π²Π»ΠΈΡΡΡ Π½Π° Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ L-Π°ΡΠΏΠ°ΡΠ°Π³ΠΈΠ½Π°Π·Ρ, Π΄ΠΎΠ±Π°Π²Π»Π΅Π½ΠΈΠ΅ ΠΈΠΎΠ½ΠΎΠ² Mn2+, Cu2+, Fe3+ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. ΠΠ΅ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΠΈ ΠΌΠ΅ΠΆΠ΄Ρ Π°Π½ΡΠΈΡΠ΅Π»ΠΎΠΌΠ΅ΡΠ°Π·Π½ΠΎΠΉ (Π°Π½ΡΠΈΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΠΎΠΉ) Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ ΠΈ ΠΊΠΈΠ½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ
ΡΠΎΡΠΌ L-Π°ΡΠΏΠ°ΡΠ°Π³ΠΈΠ½Π°Π·Ρ RrA
Solar parameters for modeling interplanetary background
The goal of the Fully Online Datacenter of Ultraviolet Emissions (FONDUE)
Working Team of the International Space Science Institute in Bern, Switzerland,
was to establish a common calibration of various UV and EUV heliospheric
observations, both spectroscopic and photometric. Realization of this goal
required an up-to-date model of spatial distribution of neutral interstellar
hydrogen in the heliosphere, and to that end, a credible model of the radiation
pressure and ionization processes was needed. This chapter describes the solar
factors shaping the distribution of neutral interstellar H in the heliosphere.
Presented are the solar Lyman-alpha flux and the solar Lyman-alpha resonant
radiation pressure force acting on neutral H atoms in the heliosphere, solar
EUV radiation and the photoionization of heliospheric hydrogen, and their
evolution in time and the still hypothetical variation with heliolatitude.
Further, solar wind and its evolution with solar activity is presented in the
context of the charge exchange ionization of heliospheric hydrogen, and in the
context of dynamic pressure variations. Also the electron ionization and its
variation with time, heliolatitude, and solar distance is presented. After a
review of all of those topics, we present an interim model of solar wind and
the other solar factors based on up-to-date in situ and remote sensing
observations of solar wind. Results of this effort will further be utilised to
improve on the model of solar wind evolution, which will be an invaluable asset
in all heliospheric measurements, including, among others, the observations of
Energetic Neutral Atoms by the Interstellar Boundary Explorer (IBEX).Comment: Chapter 2 in the planned "Cross-Calibration of Past and Present Far
UV Spectra of Solar System Objects and the Heliosphere", ISSI Scientific
Report No 12, ed. R.M. Bonnet, E. Quemerais, M. Snow, Springe
Π‘ΠΏΠΎΡΠΎΠ± ΠΏΠΎΠΈΡΠΊΠ° Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² Π΄Π»Ρ Π½ΠΎΠ²ΡΡ ΡΠ°ΠΉΡΠΎΠ² ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ
Analysis of protein structures shows that most of them have potential binding sites that may be considered as applicable for new ligand design. The lack of known ligands interacting with such binding sites seriously complicated potential ligands selection. We have developed an approach that can increase the effectiveness of virtual screening for such ligands. It integrates methods of de novo ligand design, pharmacophore modeling, molecular docking, molecular dynamics, calculation of binding energies by MM-GBSA. This approach starts by the de novo design of virtual library of potential compounds followed by selection of favourable substructures and their correct positioning in a new ligand binding site. This generated library has been used for a development of pharmacophore models that have been used for a virtual screening of molecular databases. The selected compounds were docked to the putative binding site to check their ability to accommodate into it and their ability to locate the identified favorable fragments in the same region of the binding site as de novo generated molecules. The further evaluation of the selected ligands can be carried out by standard CADD methods.ΠΠ½Π°Π»ΠΈΠ· Π±Π΅Π»ΠΊΠΎΠ²ΡΡ
ΡΡΡΡΠΊΡΡΡ ΠΏΠΎΠΊΠ°Π·ΡΠ²Π°Π΅Ρ, ΡΡΠΎ Π±ΠΎΠ»ΡΡΠΈΠ½ΡΡΠ²ΠΎ ΠΈΠ· Π½ΠΈΡ
ΠΈΠΌΠ΅ΡΡ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΠ΅ ΡΠ°ΠΉΡΡ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ, ΠΊΠΎΡΠΎΡΡΠ΅ ΠΌΠΎΠΆΠ½ΠΎ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡ ΠΊΠ°ΠΊ ΠΏΠ΅ΡΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΡΠ΅ Π΄Π»Ρ ΠΏΠΎΠΈΡΠΊΠ° Π½ΠΎΠ²ΡΡ
Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ². ΠΠ΄Π½Π°ΠΊΠΎ, ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ Π΄Π°Π½Π½ΡΡ
ΠΎ ΠΈΠ·Π²Π΅ΡΡΠ½ΡΡ
Π»ΠΈΠ³Π°Π½Π΄Π°Ρ
, Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΡ
Ρ ΡΠ°ΠΊΠΈΠΌΠΈ ΡΠ°ΠΉΡΠ°ΠΌΠΈ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ, ΡΠΈΠ»ΡΠ½ΠΎ ΠΎΠ³ΡΠ°Π½ΠΈΡΠΈΠ²Π°ΡΡ ΠΏΠΎΠΈΡΠΊΡ ΠΈ ΠΎΡΠ±ΠΎΡΡ Π½ΠΎΠ²ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ. Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ Π΄Π»Ρ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π²ΠΈΡΡΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΊΡΠΈΠ½ΠΈΠ½Π³Π°. ΠΠ°Π½Π½ΡΠΉ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ ΠΎΠ±ΡΠ΅Π΄ΠΈΠ½ΡΠ΅Ρ ΠΌΠ΅ΡΠΎΠ΄Ρ Π΄ΠΈΠ·Π°ΠΉΠ½Π° Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² de novo, ΠΏΠΎΡΡΡΠΎΠ΅Π½ΠΈΡ ΠΌΠΎΠ΄Π΅Π»Π΅ΠΉ ΡΠ°ΡΠΌΠ°ΠΊΠΎΡΠΎΡΠΎΠ², ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠΉ Π΄ΠΎΠΊΠΈΠ½Π³, ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΡ, ΡΠ°ΡΡΠ΅Ρ ΡΠ½Π΅ΡΠ³ΠΈΠΉ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ Ρ ΠΏΠΎΠΌΠΎΡΡΡ MM-GBSA. ΠΡΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠΈ Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄Π° Π½Π° ΠΏΠ΅ΡΠ²ΠΎΠΌ ΡΡΠ°ΠΏΠ΅ ΡΠΎΠ·Π΄Π°Π΅ΡΡΡ Π²ΠΈΡΡΡΠ°Π»ΡΠ½Π°Ρ Π±ΠΈΠ±Π»ΠΈΠΎΡΠ΅ΠΊΠ° ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΊΠΎΠ½ΡΡΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ de novo, Ρ ΠΏΠΎΡΠ»Π΅Π΄ΡΡΡΠΈΠΌ ΠΎΡΠ±ΠΎΡΠΎΠΌ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΡ
ΡΡΠ±ΡΡΡΡΠΊΡΡΡ ΠΈ ΠΈΡ
ΡΠ°ΡΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ Π² ΡΠ°ΠΉΡΠ΅ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ. ΠΠ° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΊΠΎΡΠΎΡΡΡ
ΡΠ°Π·ΡΠ°Π±Π°ΡΡΠ²Π°ΡΡΡΡ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΡΠ°ΡΠΌΠ°ΠΊΠΎΡΠΎΡΠΎΠ², ΠΊΠΎΡΠΎΡΡΠ΅ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΡΡΡΡ Π΄Π»Ρ Π²ΠΈΡΡΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠΊΡΠΈΠ½ΠΈΠ½Π³Π° ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ
Π±Π°Π· Π΄Π°Π½Π½ΡΡ
. ΠΡΠΎΠ±ΡΠ°Π½Π½ΡΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ Π΄ΠΎΠΊΠΈΡΡΡΡΡΡ Π² ΡΠ°ΠΉΡ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ Π΄Π»Ρ ΠΏΡΠΎΠ²Π΅ΡΠΊΠΈ ΠΈΡ
ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΡΠ°Π·ΠΌΠ΅ΡΠ°ΡΡΡΡ Π² Π½Π΅ΠΌ ΠΈ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΠΎΠ²ΠΏΠ°Π΄Π΅Π½ΠΈΡ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π±Π»Π°Π³ΠΎΠΏΡΠΈΡΡΠ½ΡΡ
ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² Π² ΡΠΎΠΌ ΠΆΠ΅ ΡΠ°ΠΉΠΎΠ½Π΅ ΡΠ°ΠΉΡΠ° ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ, ΠΏΡΠ΅Π΄ΡΠΊΠ°Π·Π°Π½Π½ΠΎΠΌ ΠΏΡΠΈ Π³Π΅Π½Π΅ΡΠ°ΡΠΈΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ» de novo. ΠΠ°Π»ΡΠ½Π΅ΠΉΡΡΡ ΠΎΡΠ΅Π½ΠΊΡ Π²ΡΠ±ΡΠ°Π½Π½ΡΡ
Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² ΠΌΠΎΠΆΠ½ΠΎ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΡΡ ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΡΠΌΠΈ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ ΠΊΠΎΠΌΠΏΡΡΡΠ΅ΡΠ½ΠΎΠ³ΠΎ ΠΊΠΎΠ½ΡΡΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π»Π΅ΠΊΠ°ΡΡΡΠ². ΠΡΠ΅Π΄Π»Π°Π³Π°Π΅ΠΌΡΠΉ ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ ΠΌΠΎΠΆΠ΅Ρ ΡΠΏΠΎΡΠΎΠ±ΡΡΠ²ΠΎΠ²Π°ΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΌΡ ΠΏΠΎΠΈΡΠΊΡ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² Π΄Π»Ρ Π½ΠΎΠ²ΡΡ
ΡΠ°ΠΉΡΠΎΠ² ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ
ΠΠ»ΠΈΡΠ½ΠΈΠ΅ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ Π³Π΅Π»Π΄Π°Π½Π°ΠΌΠΈΡΠΈΠ½Π° Ρ HSP90 Π½Π° ΡΠ°ΠΉΡ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ THR90
Prostate cancer is hormone-dependent and the androgen receptor (AR) is involved in its development. AR is a transcription factor that is activated by ligand binding, result in its translocation into the nucleus, where it initiates gene transcription. In an inactive state in cytoplasm AR exists as a complex with heat shock protein 90 (HSP90) and some other proteins. When the agonist binds, a conformational change in AR occurs, resulting in HSP90 and other chaperones dissociating. Recently it has been shown that for the dissociation of the HSP90-AR complex and the translocation of the latter into the nucleus, phosphorylation of the Thr-90 residue of the N-terminal domain of HSP90 is necessary. In this work, the effect of the HSP90 inhibitor, geldanamycin, interacting with the ATP-binding site, on the Thr90 phosphorylation site was investigated by molecular modeling methods. It has been shown that inhibitor binding slightly affects the size and mobility of cavity around Thr90. It is suggested that inhibitor binding to HSP90 does not result in changing the protein structure and does not influence on protein phosphorylation, and partially explains low effectiveness of such type of drugs in the therapy of prostate cancer.Π Π°ΠΊ ΠΏΡΠ΅Π΄ΡΡΠ°ΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ (Π ΠΠ) ΡΠ²Π»ΡΠ΅ΡΡΡ Π³ΠΎΡΠΌΠΎΠ½-Π·Π°Π²ΠΈΡΠΈΠΌΡΠΌ, Π² Π΅Π³ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎ ΡΡΠ°ΡΡΠ²ΡΠ΅Ρ Π°Π½Π΄ΡΠΎΠ³Π΅Π½ΠΎΠ²ΡΠΉ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ (AR), Π²ΡΠΏΠΎΠ»Π½ΡΡΡΠΈΠΉ ΡΠΎΠ»Ρ ΡΠ°ΠΊΡΠΎΡΠ° ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΈ. Π Π½Π΅Π°ΠΊΡΠΈΠ²Π½ΠΎΠΌ ΡΠΎΡΡΠΎΡΠ½ΠΈΠΈ Π² ΡΠΈΡΠΎΠ·ΠΎΠ»Π΅ AR Π½Π°Ρ
ΠΎΠ΄ΠΈΡΡΡ Π² ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ΅ Ρ Π±Π΅Π»ΠΊΠΎΠΌ ΡΠ΅ΠΏΠ»ΠΎΠ²ΠΎΠ³ΠΎ ΡΠΎΠΊΠ° HSP90 ΠΈ ΡΡΠ΄ΠΎΠΌ Π΄ΡΡΠ³ΠΈΡ
Π±Π΅Π»ΠΊΠΎΠ². ΠΠ·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Ρ Π°Π³ΠΎΠ½ΠΈΡΡΠΎΠΌ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΊΠΎΠ½ΡΠΎΡΠΌΠ°ΡΠΈΠΎΠ½Π½ΡΠΌ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡΠΌ Π² AR, Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΠ΅Π³ΠΎ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡ AR Ρ ΡΠ°ΠΏΠ΅ΡΠΎΠ½Π°ΠΌΠΈ ΡΠ°ΡΠΏΠ°Π΄Π°Π΅ΡΡΡ ΠΈ AR ΡΡΠ°Π½ΡΠΏΠΎΡΡΠΈΡΡΠ΅ΡΡΡ Π² ΡΠ΄ΡΠΎ. ΠΠ΅Π΄Π°Π²Π½ΠΎ Π±ΡΠ»ΠΎ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΎ, ΡΡΠΎ Π΄Π»Ρ Π΄ΠΈΡΡΠΎΡΠΈΠ°ΡΠΈΠΈ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ° ΡΠ°ΠΏΠ΅ΡΠΎΠ½Π° HSP90 ΠΈ AR Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΎΡΡΠ°ΡΠΊΠ° Thr-90 N-ΠΊΠΎΠ½ΡΠ΅Π²ΠΎΠ³ΠΎ Π΄ΠΎΠΌΠ΅Π½Π° HSP90. Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠ³ΠΎ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠ΅ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° HSP90 Π³Π΅Π»Π΄Π°Π½Π°ΠΌΠΈΡΠΈΠ½Π°, Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΡΡΡΠ΅Π³ΠΎ Ρ ΠΠ’Π -ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΠΌ ΡΠ°ΠΉΡΠΎΠΌ, Π½Π° ΡΠ°ΠΉΡ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Thr90. ΠΡΠ»ΠΎ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° Π½Π΅ ΡΠΈΠ»ΡΠ½ΠΎ Π²Π»ΠΈΡΠ΅Ρ Π½Π° ΡΠ°Π·ΠΌΠ΅Ρ ΠΈ ΠΏΠΎΠ΄Π²ΠΈΠΆΠ½ΠΎΡΡΡ Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡΠ½ΡΡ
ΠΎΡΡΠ°ΡΠΊΠΎΠ² ΠΏΠΎΠ»ΠΎΡΡΠΈ ΠΎΠΊΠΎΠ»ΠΎ Thr90. ΠΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°Π΅ΡΡΡ, ΡΡΠΎ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° Ρ HSP90 Π½Π΅ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΡΡΡΠΊΡΡΡΡ Π±Π΅Π»ΠΊΠ° ΠΈ Π½Π΅ ΠΌΠΎΠΆΠ΅Ρ Π²Π»ΠΈΡΡΡ Π½Π° Π΅Π³ΠΎ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅, ΡΡΠΎ ΠΎΡΡΠ°ΡΡΠΈ ΠΌΠΎΠΆΠ΅Ρ ΠΎΠ±ΡΡΡΠ½ΠΈΡΡ Π½Π΅Π²ΡΡΠΎΠΊΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠ°ΠΊΠΎΠ³ΠΎ ΡΠΈΠΏΠ° ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² Π² Ρ
ΠΈΠΌΠΈΠΎΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π ΠΠ
ΠΠΎΠ½ΡΡΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΈ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ Ρ ΠΈΠΌΠ΅ΡΠ½ΠΎΠ³ΠΎ Π³Π΅Π½Π° ΡΠ΅Π½Π°Π»Π°Π·Ρ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°, ΠΊΠΎΠ΄ΠΈΡΡΡΡΠ΅Π³ΠΎ N-ΠΊΠΎΠ½ΡΠ΅Π²ΡΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΡΠ΅ΠΊΡΠ΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ Π±Π΅Π»ΠΊΠ° ΠΏΡΠΎΠ»Π°ΠΊΡΠΈΠ½Π°
Renalase (RNLS) is a protein that performs various protective functions both inside and outside cells. Intracellular RNLS is a FAD-dependent oxidoreductase (EC 1.6.3.5). Extracellular RNLS lacking an N-terminal peptide does not interact with FAD and exhibits various protective effects on the cell through interaction with receptor proteins. The mechanisms and factors responsible for RNLS transport out of the cell are not fully understood. It is well known that the signal sequence plays a key role in the classical mechanism of protein transport outside cells. One of the approaches to study the secretion of RNLS from the cell can be the creation of chimeric forms of the protein with a modified N-terminal amino acid signal sequence. Bioinformatics analysis showed that the signal sequence of the prolactin gene (PRL), connected to the template sequence of the RNLS gene, gave the classic signal characteristic of secretory proteins. On this basis, this paper describes: (i) a method for constructing the human RNLS gene in which the N-terminal sequence encoded by the RNLS gene was replaced by the N-terminal sequence encoded by the PRL gene; (ii) expression of this chimeric genetic construct.Π Π΅Π½Π°Π»Π°Π·Π° (RNLS) - Π±Π΅Π»ΠΎΠΊ, ΠΊΠΎΡΠΎΡΡΠΉ Π²ΡΠΏΠΎΠ»Π½ΡΠ΅Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ Π·Π°ΡΠΈΡΠ½ΡΠ΅ ΡΡΠ½ΠΊΡΠΈΠΈ ΠΊΠ°ΠΊ Π²Π½ΡΡΡΠΈ, ΡΠ°ΠΊ ΠΈ ΡΠ½Π°ΡΡΠΆΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ. ΠΠ½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½Π°Ρ RNLS ΠΏΡΠΎΡΠ²Π»ΡΠ΅Ρ ΡΠ²ΠΎΠΉΡΡΠ²Π° FAD-Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠΉ ΠΎΠΊΡΠΈΠ΄ΠΎΡΠ΅Π΄ΡΠΊΡΠ°Π·Ρ (ΠΠ€ 1.6.3.5). ΠΠ½Π΅ΠΊΠ»Π΅ΡΠΎΡΠ½Π°Ρ RNLS, Π»ΠΈΡΠ΅Π½Π½Π°Ρ N-ΠΊΠΎΠ½ΡΠ΅Π²ΠΎΠ³ΠΎ ΠΏΠ΅ΠΏΡΠΈΠ΄Π°, Π½Π΅ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΡΠ΅Ρ Ρ FAD, ΠΏΡΠΎΡΠ²Π»ΡΠ΅Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ Π·Π°ΡΠΈΡΠ½ΡΠ΅ ΡΡΡΠ΅ΠΊΡΡ Π½Π° ΠΊΠ»Π΅ΡΠΊΡ ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ Π½Π° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΠ΅ Π±Π΅Π»ΠΊΠΈ. ΠΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΡ ΠΈ ΡΠ°ΠΊΡΠΎΡΡ, ΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΡΠ΅ Π·Π° ΡΡΠ°Π½ΡΠΏΠΎΡΡ RNLS ΠΈΠ· ΠΊΠ»Π΅ΡΠΊΠΈ, Π΄ΠΎ ΠΊΠΎΠ½ΡΠ° Π½Π΅ ΠΈΠ·ΡΡΠ΅Π½Ρ. Π₯ΠΎΡΠΎΡΠΎ ΠΈΠ·Π²Π΅ΡΡΠ½ΠΎ, ΡΡΠΎ ΡΠΈΠ³Π½Π°Π»ΡΠ½Π°Ρ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΈΠ³ΡΠ°Π΅Ρ ΠΊΠ»ΡΡΠ΅Π²ΡΡ ΡΠΎΠ»Ρ Π² ΠΊΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠ΅ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ° Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
Π±Π΅Π»ΠΊΠΎΠ². ΠΠ΄Π½ΠΈΠΌ ΠΈΠ· ΠΏΠΎΠ΄Ρ
ΠΎΠ΄ΠΎΠ² Π΄Π»Ρ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΡΠ΅ΠΊΡΠ΅ΡΠΈΠΈ RNLS ΠΈΠ· ΠΊΠ»Π΅ΡΠΊΠΈ ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΡΠΎΠ·Π΄Π°Π½ΠΈΠ΅ Ρ
ΠΈΠΌΠ΅ΡΠ½ΡΡ
ΡΠΎΡΠΌ Π±Π΅Π»ΠΊΠ° Ρ ΠΌΠΎΠ΄ΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ N-ΠΊΠΎΠ½ΡΠ΅Π²ΠΎΠΉ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΠΎΠΉ Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡΠ½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ. ΠΠΈΠΎΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ ΡΠΈΠ³Π½Π°Π»ΡΠ½Π°Ρ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ Π³Π΅Π½Π° ΠΏΡΠΎΠ»Π°ΠΊΡΠΈΠ½Π° (PRL), ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½Π½Π°Ρ Ρ ΠΌΠ°ΡΡΠΈΡΠ½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡΡ Π³Π΅Π½Π° RNLS, Π΄Π°Π²Π°Π»Π° ΠΊΠ»Π°ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠΈΠ³Π½Π°Π», ΡΠ²ΠΎΠΉΡΡΠ²Π΅Π½Π½ΡΠΉ ΡΠ΅ΠΊΡΠ΅ΡΠΎΡΠ½ΡΠΌ Π±Π΅Π»ΠΊΠ°ΠΌ. ΠΡΡ
ΠΎΠ΄Ρ ΠΈΠ· ΡΡΠΎΠ³ΠΎ, Π² Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅: (i) ΠΎΠΏΠΈΡΠ°Π½ ΠΌΠ΅ΡΠΎΠ΄ ΠΊΠΎΠ½ΡΡΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π³Π΅Π½Π° RNLS ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°, Π² ΠΊΠΎΡΠΎΡΠΎΠΌ N-ΠΊΠΎΠ½ΡΠ΅Π²Π°Ρ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ, ΠΊΠΎΠ΄ΠΈΡΡΠ΅ΠΌΠ°Ρ Π³Π΅Π½ΠΎΠΌ RNLS, Π±ΡΠ»Π° Π·Π°ΠΌΠ΅Π½Π΅Π½Π° Π½Π° N-ΠΊΠΎΠ½ΡΠ΅Π²ΡΡ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ, ΠΊΠΎΠ΄ΠΈΡΡΠ΅ΠΌΡΡ Π³Π΅Π½ΠΎΠΌ PRL; (ii) ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π° ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΡΠΎΠΉ Ρ
ΠΈΠΌΠ΅ΡΠ½ΠΎΠΉ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΈ
Experiment with the SPR-N Instrument Onboard the CORONAS-F Satellite: Polarization, Temporal, and Spectral Characteristics of the Hard X-Ray of the Solar Flares
Toxin-antitoxin systems: A tool for taxonomic analysis of human intestinal microbiota
The human gastrointestinal microbiota (HGM) is known for its rich diversity of bacterial species and strains. Yet many studies stop at characterizing theHGMat the family level. This is mainly due to lack of adequate methods for a high-resolution profiling of the HGM. One way to characterize the strain diversity of the HGM is to look for strain-specific functional markers. Here, we propose using type II toxin-antitoxin systems (TAS). To identify TAS systems in the HGM, we previously developed the software TAGMA. This software was designed to detect the TAS systems, MazEF and RelBE, in lactobacilli and bifidobacteria. In this study, we updated the gene catalog created previously and used it to test our software anew on 1346 strains of bacteria, which belonged to 489 species and 49 genera. We also sequenced the genomes of 20 fecal samples and analyzed the results with TAGMA. Although some differences were detected at the strain level, the results showed no particular difference in the bacterial species between our method and other classic analysis software. These results support the use of the updated catalog of genes encoding type II TAS as a useful tool for computer-assisted species and strain characterization of the HGM. Β© 2020 by the authors