Π£ΡΠ΅Ρ Π³ΠΈΠ΄ΡΠΎΡΠΎΠ±Π½ΡΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠΉ ΠΏΡΠΈ ΠΎΡΠ΅Π½ΠΊΠ΅ ΠΏΡΠΎΡΡΡΠ°Π½ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΡΡΡΡΠΊΡΡΡΡ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π½ΡΡ Π±Π΅Π»ΠΊΠΎΠ² ΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅ Π΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΡ Π½Π° Π½ΠΈΡ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ²
Palczewski, K., Kumasaka, T., Hon, T., Behnke, C.A., Motoshima, H., Fox, B.A., Le Trong, I., Teller, D.C., Okada, T., Stenkamp, R.E., Yamamoto, M., Miyano, M. (2000). Crystal Structure of Rhodopsin: A G-Protein-Coupled Receptor. Science 289, 739β745. Louis, S.N., Nero, T.L., Iakovidis, D., Coiagrande, F.M., Jackman, G.P., Louis, W.J. (1999). beta (l) — and beta (2)-Adrenoceptor antagonist… Π§ΠΈΡΠ°ΡΡ Π΅ΡΡ >
Π£ΡΠ΅Ρ Π³ΠΈΠ΄ΡΠΎΡΠΎΠ±Π½ΡΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠΉ ΠΏΡΠΈ ΠΎΡΠ΅Π½ΠΊΠ΅ ΠΏΡΠΎΡΡΡΠ°Π½ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΡΡΡΡΠΊΡΡΡΡ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π½ΡΡ Π±Π΅Π»ΠΊΠΎΠ² ΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠ΅ Π΄Π΅ΠΉΡΡΠ²ΡΡΡΠΈΡ Π½Π° Π½ΠΈΡ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² (ΡΠ΅ΡΠ΅ΡΠ°Ρ, ΠΊΡΡΡΠΎΠ²Π°Ρ, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½Π°Ρ)
Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- Π‘ΠΏΠΈΡΠΎΠΊ ΡΠΎΠΊΡΠ°ΡΠ΅Π½ΠΈΠΉ
- ΠΠ»Π°Π²Π° 1.
- ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅
- ΠΠ»Π°Π²Π° 2. ΠΠ΅ΡΠΎΠ΄Ρ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΡΡΠΊΡΡΡΡ GPCR, ΠΎΡΠ΅Π½ΠΊΠΈ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° ΡΠΏΠ°ΠΊΠΎΠ²ΠΊΠΈ Π±Π΅Π»ΠΊΠΎΠ²ΡΡ
ΡΡΡΡΠΊΡΡΡ ΠΈ ΠΏΡΠ΅Π΄ΡΠΊΠ°Π·Π°Π½ΠΈΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π½ΠΈΠ·ΠΊΠΎΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ (ΠΎΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ)
- 2. 1. ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΡΡΡΠ°Π½ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΡΡΡΡΠΊΡΡΡΡ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π½ΡΡ Π±Π΅Π»ΠΊΠΎΠ²
- 2. 2. Π Π°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΡΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° GPCR
- 2. 2. L. ΠΠ±ΡΠ°Ρ ΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΡ ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°Ρ
GPCR
- 2. 2. 2. ΠΠ΅ΡΠΎΠ΄Ρ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ab initio
- 2. 2. 3. ΠΠ΅ΡΠΎΠ΄Ρ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ Π³ΠΎΠΌΠΎΠ»ΠΎΠ³ΠΈΠΈ
- 2. 3. Π‘ΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΠΊΠ°ΡΠ΅ΡΡΠ²Π° ΡΠΏΠ°ΠΊΠΎΠ²ΠΊΠΈ Π±Π΅Π»ΠΊΠΎΠ²
- 2. 4. ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½Π°Ρ Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠ° ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π½ΡΡ
Π±Π΅Π»ΠΊΠΎΠ²
- 2. 4. 1. ΠΠΎΠ»Π½ΠΎΠ°ΡΠΎΠΌΠ½ΠΎΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠΎΠ²ΡΡ ΡΡΡΡΠΊΡΡΡ
- 2. 4. 2. ΠΡΡΠΏΠ½ΠΎΠ·Π΅ΡΠ½ΠΈΡΡΠΎΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠΎΠ²ΡΡ ΡΡΡΡΠΊΡΡΡ
- 2. 5. Π Π°ΡΡΠ΅Ρ Π³ΠΈΠ΄ΡΠΎΡΠΎΠ±Π½ΡΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠΉ
- 2. 6. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠΉ «ΡΡΡΡΠΊΡΡΡΠ° — Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ» Π΄Π»Ρ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² Π±Π΅ΡΠ°2-Π°Π΄ΡΠ΅Π½ΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°
- 2. 6. 1. ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠ΅ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π²Π»ΠΈΡΠ½ΠΈΡ ΡΡΡΡΠΊΡΡΡΡ Π½Π° Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ
- 2. 6. 2. ΠΠΎΠΌΠΏΡΡΡΠ΅ΡΠ½ΡΠΉ ΠΏΠΎΠΈΡΠΊ Π°ΠΊΡΠΈΠ²Π½ΡΡ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ
- 3. 1. Π Π°Π·ΡΠ°Π±ΠΎΡΠΊΠ° ΠΈ ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΎΡΠ΅Π½ΠΎΡΠ½ΡΡ
ΡΡΠ½ΠΊΡΠΈΠΉ Π΄Π»Ρ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π½ΡΡ
Π±Π΅Π»ΠΊΠΎΠ²
- 3. 1. 1. ΠΠ½Π°Π»ΠΈΠ· ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π½ΡΡ ΡΡΡΡΠΊΡΡΡ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π½ΡΡ Π±Π΅Π»ΠΊΠΎΠ²
- 3. 1. 2. ΠΡΡΠΏΠ½ΠΎΠ·Π΅ΡΠ½ΠΈΡΡΠ°Ρ ΠΈ ΠΏΠΎΠ»Π½ΠΎΠ°ΡΠΎΠΌΠ½Π°Ρ ΠΎΡΠ΅Π½ΠΎΡΠ½ΡΠ΅ ΡΡΠ½ΠΊΡΠΈΠΈ
- 3. 1. 3. ΠΠ΄Π΅Π½ΡΠΈΡΠΈΠΊΠ°ΡΠΈΡ ΠΊΡΠΈΡΡΠ°Π»Π»ΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΡΡΡΠΊΡΡΡΡ ΡΠΎΠ΄ΠΎΠΏΡΠΈΠ½Π° ΡΡΠ΅Π΄ΠΈ Π½Π°Π±ΠΎΡΠ° Π½Π΅ΡΠΎΡΠ½ΡΡ ΠΌΠΎΠ΄Π΅Π»Π΅ΠΉ
- 3. 1. 4. Π€ΠΎΡΠΌΡΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΡΠΈΡΠ΅ΡΠΈΡ ΠΊΠΎΡΡΠ΅ΠΊΡΠ½ΠΎΡΡΠΈ ΡΡΡΡΠΊΡΡΡ ΠΠ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΎΡΠ΅Π½ΠΎΡΠ½ΡΡ ΡΡΠ½ΠΊΡΠΈΠΉ
- 3. 1. 5. ΠΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΎΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΠΈ ΠΌΠΎΠ΄Π΅Π»Π΅ΠΉ Ρ ΠΏΡΠ°Π²ΠΈΠ»ΡΠ½ΠΎΠΉ ΡΠΊΠ»Π°Π΄ΠΊΠΎΠΉ ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΉ ΡΠ΅ΠΏΠΈ
- 3. 1. 6. ΠΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΎΡΠΈΠ±ΠΎΠΊ Π² Π²ΡΡΠ°Π²Π½ΠΈΠ²Π°Π½ΠΈΠΈ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΡΡ ΠΎΡΠ΅Π½ΠΎΡΠ½ΡΡ ΡΡΠ½ΠΊΡΠΈΠΉ
- 3. 1. 7. Π‘ΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π½ΡΡ ΠΎΡΠ΅Π½ΠΎΡΠ½ΡΡ ΡΡΠ½ΠΊΡΠΈΠΉ Ρ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΠΌΠΈ
- 3. 2. ΠΠΈΠ΄ΡΠΎΡΠΎΠ±Π½Π°Ρ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΌΠ΅Π½ΡΠ°ΡΠ½ΠΎΡΡΡ Π±Π΅ΡΠ°-Π±Π»ΠΎΠΊΠ°ΡΠΎΡΠΎΠ² Π² ΡΠ°ΠΉΡΠ΅ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ Ρ2-Π°Π΄ΡΠ΅Π½ΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΈ Π΅Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ Π΄Π»Ρ ΠΏΡΠ΅Π΄ΡΠΊΠ°Π·Π°Π½ΠΈΡ ΠΊΠΎΠ½ΡΡΠ°Π½ΡΡ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ
- 3. 2. 1. ΠΠ½Π°Π»ΠΈΠ· Π³ΠΈΠ΄ΡΠΎΡΠΎΠ±Π½ΠΎΠΉ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΠΈ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² Π²Π Π‘Π― Ρ Π»ΠΈΠ³Π°Π½Π΄Π°ΠΌΠΈ
- 3. 2. 2. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ Π΄ΠΎΠΊΠΈΠ½Π³Π° Π±Π΅ΡΠ°-Π±Π»ΠΎΠΊΠ°ΡΠΎΡΠΎΠ²
- 3. 2. 3. ΠΠΎΠΌΠΏΠ»Π΅ΠΌΠ΅Π½ΡΠ°ΡΠ½ΠΎΡΡΡ Π³ΠΈΠ΄ΡΠΎΡΠΎΠ±Π½ΡΡ ΡΠ²ΠΎΠΉΡΡΠ² Π² ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ°Ρ Π±Π΅ΡΠ°-Π±Π»ΠΎΠΊΠ°ΡΠΎΡΠΎΠ²
- 3. 2. 4. Π€ΡΠ°Π³ΠΌΠ΅Π½ΡΠ°ΡΠ½Π°Ρ ΡΡΠ½ΠΊΡΠΈΡ ΡΠ°ΡΡΠ΅ΡΠ° Π°ΡΡΠΈΠ½Π½ΠΎΡΡΠΈ
- 3. 2. 5. ΠΠΎΠΈΡΠΊ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Ρ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎ Π²ΡΡΠΎΠΊΠΎΠΉ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΡΡ
- 3. 2. 6. Π‘ΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ ΠΏΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½Π½ΠΎΠ³ΠΎ ΠΌΠ΅ΡΠΎΠ΄Π° ΠΏΡΠ΅Π΄ΡΠΊΠ°Π·Π°Π½ΠΈΡ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΠΈ Ρ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΠΌΠΈ
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