Π”ΠΈΠΏΠ»ΠΎΠΌ, курсовая, ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½Π°Ρ Ρ€Π°Π±ΠΎΡ‚Π°
ΠŸΠΎΠΌΠΎΡ‰ΡŒ Π² написании студСнчСских Ρ€Π°Π±ΠΎΡ‚

РСализация Π°Π»Π³ΠΎΡ€ΠΈΡ‚ΠΌΠΎΠ² ΠΊΠΎΠΌΠ±ΠΈΠ½ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Ρ… ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠ² ΠΊΠ²Π°Π½Ρ‚ΠΎΠ²ΠΎΠΉ ΠΈ молСкулярной ΠΌΠ΅Ρ…Π°Π½ΠΈΠΊΠΈ ΠΈ прилоТСния ΠΊ исслСдованиям ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΠΎΠ² Ρ€Π΅Π°ΠΊΡ†ΠΈΠΉ Π² растворах ΠΈ биологичСских систСмах

Π”ΠΈΡΡΠ΅Ρ€Ρ‚Π°Ρ†ΠΈΡΠŸΠΎΠΌΠΎΡ‰ΡŒ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈΠ£Π·Π½Π°Ρ‚ΡŒ ΡΡ‚ΠΎΠΈΠΌΠΎΡΡ‚ΡŒΠΌΠΎΠ΅ΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹

КаТдая ΠΈΠ· Ρ€Π°ΡΡΠΌΠΎΡ‚Ρ€Π΅Π½Π½Ρ‹Ρ… систСм прСдставляСт интСрСс для ΡΠΎΠΎΡ‚Π²Π΅Ρ‚ΡΡ‚Π²ΡƒΡŽΡ‰Π΅ΠΉ области Π±ΠΈΠΎΡ„ΠΈΠ·ΠΈΠΊΠΈ (Π±ΠΈΠΎΡ…ΠΈΠΌΠΈΠΈ), Π½ΠΎ Π΄Π»Ρ Ρ†Π΅Π»Π΅ΠΉ Π΄Π°Π½Π½ΠΎΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹ Ρ‚Π°ΠΊΠΆΠ΅ Π²Π°ΠΆΠ½ΠΎ Π±Ρ‹Π»ΠΎ ΡƒΡΡ‚Π°Π½ΠΎΠ²ΠΈΡ‚ΡŒ, насколько эффСктивно ΠΏΡ€ΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π΄Π°Π½Π½ΠΎΠΉ Ρ€Π΅Π°Π»ΠΈΠ·Π°Ρ†ΠΈΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° КМ/ММ. Π‘ ΡΡ‚ΠΎΠΉ Ρ†Π΅Π»ΡŒΡŽ Π² Ρ€ΡΠ΄Π΅ ΠΏΡ€ΠΈΠΌΠ΅Ρ€ΠΎΠ² ΠΏΡ€ΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΎΡΡŒ сравнСниС Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚ΠΎΠ² Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… Π²Π°Ρ€ΠΈΠ°Π½Ρ‚ΠΎΠ² КМ/ММ. Π’ΠΎ Π²ΡΠ΅Ρ… случаях расчСты Π²Ρ‹ΠΏΠΎΠ»Π½ΡΠ»ΠΈΡΡŒ Π½Π° ΡΡƒΠΏΠ΅Ρ€ΠΊΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€Π½Ρ‹Ρ… рСсурсах ΠœΠ“Π£ ΠΈΠΌ. Πœ. Π’… Π§ΠΈΡ‚Π°Ρ‚ΡŒ Π΅Ρ‰Ρ‘ >

Π‘ΠΎΠ΄Π΅Ρ€ΠΆΠ°Π½ΠΈΠ΅

  • Π“Π»Π°Π²Π° 1. Π›ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Π½Ρ‹ΠΉ ΠΎΠ±Π·ΠΎΡ€. ΠšΠΎΠΌΠ±ΠΈΠ½ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Π΅ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹ ΠΊΠ²Π°Π½Ρ‚ΠΎΠ²ΠΎΠΉ ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»ΡΡ€Π½ΠΎΠΉ ΠΌΠ΅Ρ…Π°Π½ΠΈΠΊΠΈ
    • 1. 1. ΠžΠ±Ρ‰ΠΈΠ΅ свСдСния
    • 1. 2. ΠœΠ΅Ρ‚ΠΎΠ΄ КМ/ММ
      • 1. 2. 1. ВСрминология
      • 1. 2. 2. Полная энСргия Π² ΠΌΠ΅Ρ‚ΠΎΠ΄Π΅ КМ/ММ
      • 1. 2. 3. ΠœΠ΅Ρ…Π°Π½ΠΈΡ‡Π΅ΡΠΊΠΎΠ΅ Π²Π½Π΅Π΄Ρ€Π΅Π½ΠΈΠ΅
      • 1. 2. 3. ЭлСктростатичСскоС Π²Π½Π΅Π΄Ρ€Π΅Π½ΠΈΠ΅
      • 1. 2. 4. ΠŸΠΎΠ»ΡΡ€ΠΈΠ·Π°Ρ†ΠΈΠΎΠ½Π½ΠΎΠ΅ Π²Π½Π΅Π΄Ρ€Π΅Π½ΠΈΠ΅
    • 1. 3. Π”Ρ€ΡƒΠ³ΠΈΠ΅ взаимодСйствия, ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΡƒΠ΅ΠΌΡ‹Π΅ Π² ΠšΠœ/ММ схСмах
      • 1. 3. 1. Π”Π°Π»ΡŒΠ½ΠΎΠ΄Π΅ΠΉΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΠ΅ элСктростатичСскиС взаимодСйствия
      • 1. 3. 2. Π’Π°Π½-Π΄Π΅Ρ€-Π²Π°Π°Π»ΡŒΡΠΎΠ²Ρ‹Π΅ взаимодСйствия Π² ΠΌΠ΅Ρ‚ΠΎΠ΄Π΅ КМ/ММ
      • 1. 3. 3. БвязанныС КМ/ММ взаимодСйствия
    • 1. 4. Π Π°Π·Ρ€Ρ‹Π² ΠΌΠ΅ΠΆΠ΄Ρƒ ΠšΠœ ΠΈ ΠœΠœ подсистСмами ΠΏΠΎ ΠΊΠΎΠ²Π°Π»Π΅Π½Ρ‚Π½ΠΎΠΉ связи
      • 1. 4. 1. ΠžΠ±Π·ΠΎΡ€ ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠ²
      • 1. 4. 2. Π’Ρ‹Π±ΠΎΡ€ мСста Ρ€Π°Π·Ρ€Ρ‹Π²Π°
      • 1. 4. 3. LINK-Π°Ρ‚ΠΎΠΌΡ‹
      • 1. 4. 4. Π‘Π²ΡΠ·Ρ‹Π²Π°ΡŽΡ‰ΠΈΠ΅ Π°Ρ‚ΠΎΠΌΡ‹
      • 1. 4. 4. Π—Π°ΠΌΠΎΡ€ΠΎΠΆΠ΅Π½Π½Ρ‹Π΅ Π»ΠΎΠΊΠ°Π»ΠΈΠ·ΠΎΠ²Π°Π½Π½Ρ‹Π΅ ΠΎΡ€Π±ΠΈΡ‚Π°Π»ΠΈ
    • 1. 5. ΠŸΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌΠ½Ρ‹Π΅ Ρ€Π΅Π°Π»ΠΈΠ·Π°Ρ†ΠΈΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° КМ/ММ
    • 1. 6. ΠœΠ΅Ρ‚ΠΎΠ΄ ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π»ΠΎΠ² эффСктивных Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚ΠΎΠ²
  • Π“Π»Π°Π²Π° 2. ΠœΠ΅Ρ‚ΠΎΠ΄ ΠΊΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΎΠ½Π½ΠΎ-ΠΏΠΎΠ΄Π²ΠΈΠΆΠ½Ρ‹Ρ… эффСктивных Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚ΠΎΠ²
    • 2. 1. Π’Π²Π΅Π΄Π΅Π½ΠΈΠ΅
    • 2. 2. ΠšΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΎΠ½Π½ΠΎ-ΠΏΠΎΠ΄Π²ΠΈΠΆΠ½Ρ‹Π΅ ТёсткиС Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚Ρ‹
    • 2. 3. ЭлСктростатичСскоС взаимодСйствиС
    • 2. 4. Π Π°Π·Ρ€Ρ‹Π² ΠΏΠΎ ΠΊΠΎΠ²Π°Π»Π΅Π½Ρ‚Π½ΠΎΠΉ связи
    • 2. 5. Расчёт сил взаимодСйствия КМ/ММ
    • 2. 6. РСализация ΠΌΠ΅Ρ‚ΠΎΠ΄Π° ΠΊΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΎΠ½Π½ΠΎ-ΠΏΠΎΠ΄Π²ΠΈΠΆΠ½Ρ‹Ρ… эффСктивных Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚ΠΎΠ²
  • Π“Π»Π°Π²Π° 3. ΠœΠΎΠ΄Π΅Π»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ Π³ΠΈΠ΄Ρ€ΠΎΠ»ΠΈΠ·Π° цикличСского гуанозинмонофосфата Π² Π²ΠΎΠ΄Π½ΠΎΠΌ растворС
    • 3. 1. Π’Π²Π΅Π΄Π΅Π½ΠΈΠ΅
    • 3. 2. ЦикличСский гуанозинмонофосфат (Ρ†Π“ΠœΠ€)
    • 3. 3. ΠŸΡ€ΠΎΡ‚ΠΎΠΊΠΎΠ» вычислСний
    • 3. 4. Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ модСлирования
    • 3. 5. ΠžΠ±ΡΡƒΠΆΠ΄Π΅Π½ΠΈΠ΅ Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚ΠΎΠ²
  • Π“Π»Π°Π²Π° 4. ΠœΠΎΠ΄Π΅Π»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ Π³ΠΈΠ΄Ρ€ΠΎΠ»ΠΈΠ·Π° Π°Ρ†Π΅Ρ‚ΠΈΠ»Ρ…ΠΎΠ»ΠΈΠ½Π° Π² Π°ΠΊΡ‚ΠΈΠ²Π½ΠΎΠΌ Ρ†Π΅Π½Ρ‚Ρ€Π΅ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π° ацСтилхолинэстСразы
    • 4. 1. Π€Π΅Ρ€ΠΌΠ΅Π½Ρ‚ ацСтилхолинэстСраза
    • 4. 2. МодСльная систСма ΠΈ ΠΏΡ€ΠΎΡ‚ΠΎΠΊΠΎΠ» вычислСний
    • 4. 3. Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ модСлирования
    • 4. 4. ΠžΠ±ΡΡƒΠΆΠ΄Π΅Π½ΠΈΠ΅ Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚ΠΎΠ²
      • 4. 4. 1. Роль ΠΊΠ²Π°Π½Ρ‚ΠΎΠ²ΠΎ-химичСского ΠΌΠ΅Ρ‚ΠΎΠ΄Π° ΠΈ ΠšΠœ/ММ раздСлСния систСмы
      • 4. 4. 2. Роль Π½Π°Ρ‡Π°Π»ΡŒΠ½ΠΎΠΉ кристалличСской структуры
      • 4. 4. 3. Π‘Ρ€Π°Π²Π½Π΅Π½ΠΈΠ΅ Π΄Π²ΡƒΡ… Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠ² КМ/ММ
  • Π“Π»Π°Π²Π° 5. ΠœΠΎΠ΄Π΅Π»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ дСкарбоксилирования Π·Π΅Π»Ρ‘Π½ΠΎΠ³ΠΎ флуорСсцСнтного Π±Π΅Π»ΠΊΠ° (ΠžΠ‘Π )
    • 5. 1. Π—Π΅Π»Ρ‘Π½Ρ‹ΠΉ флуорСсцСнтный Π±Π΅Π»ΠΎΠΊ (Π²Π Π )
    • 5. 2. ЀоторСакция дСкарбоксилирования Π²Π‘Π 
    • 5. 3. МодСльная систСма ΠΈ ΠΏΡ€ΠΎΡ‚ΠΎΠΊΠΎΠ» вычислСний
    • 5. 4. Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ модСлирования
      • 5. 4. 1. Π­Π»Π΅ΠΊΡ‚Ρ€ΠΎΠ½Π½Ρ‹ΠΉ ΠΏΠ΅Ρ€Π΅Ρ…ΠΎΠ΄ 80−81 Π² Πœ-ΠžΠ‘Π 
      • 5. 4. 2. Π­Π»Π΅ΠΊΡ‚Ρ€ΠΎΠ½Π½Ρ‹Π΅ ΠΏΠ΅Ρ€Π΅Ρ…ΠΎΠ΄Ρ‹ 8ΠΎ-8ΠΏ (ΠΏ>1) Π² Π½Π΅ΠΉΡ‚Ρ€Π°Π»ΡŒΠ½ΠΎΠΌ Ρ…Ρ€ΠΎΠΌΠΎΡ„ΠΎΡ€Π΅ vt-GFPl
      • 5. 4. 3. ВозбуТдСния Π½Π° ΡƒΡ€ΠΎΠ²Π½ΠΈ с ΠΏΠ΅Ρ€Π΅Π½ΠΎΡΠΎΠΌ элСктрона 8Π‘Π’
      • 5. 4. 4. ВлияниС ΠΌΡƒΡ‚Π°Ρ†ΠΈΠΈ ΠŸΠΈΠ—ΠžΠ—Π˜Π²
    • 5. 5. Π’ΠΎΠ·ΠΌΠΎΠΆΠ½Ρ‹Π΅ ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΡ‹ процСсса дСкарбоксилирования vt-GFP
  • Π’Ρ‹Π²ΠΎΠ΄Ρ‹

РСализация Π°Π»Π³ΠΎΡ€ΠΈΡ‚ΠΌΠΎΠ² ΠΊΠΎΠΌΠ±ΠΈΠ½ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Ρ… ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠ² ΠΊΠ²Π°Π½Ρ‚ΠΎΠ²ΠΎΠΉ ΠΈ молСкулярной ΠΌΠ΅Ρ…Π°Π½ΠΈΠΊΠΈ ΠΈ прилоТСния ΠΊ исслСдованиям ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΠΎΠ² Ρ€Π΅Π°ΠΊΡ†ΠΈΠΉ Π² растворах ΠΈ биологичСских систСмах (Ρ€Π΅Ρ„Π΅Ρ€Π°Ρ‚, курсовая, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½Π°Ρ)

Π‘ΠΎΠ²Ρ€Π΅ΠΌΠ΅Π½Π½Ρ‹Π΅ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹ ΠΊΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€Π½ΠΎΠ³ΠΎ модСлирования ΠΎΠΊΠ°Π·Ρ‹Π²Π°ΡŽΡ‚ ΡΡƒΡ‰Π΅ΡΡ‚Π²Π΅Π½Π½ΡƒΡŽ ΠΏΠΎΠ΄Π΄Π΅Ρ€ΠΆΠΊΡƒ ΡΠΊΡΠΏΠ΅Ρ€ΠΈΠΌΠ΅Π½Ρ‚Π°Π»ΡŒΠ½Ρ‹ΠΌ исслСдованиям слоТных биомолСкулярных систСм, позволяя Ρ€Π°ΡΡΡ‡ΠΈΡ‚Ρ‹Π²Π°Ρ‚ΡŒ гСомСтричСскиС ΠΏΠ°Ρ€Π°ΠΌΠ΅Ρ‚Ρ€Ρ‹ Π±ΠΈΠΎΠΌΠΎΠ»Π΅ΠΊΡƒΠ», ΠΎΡ†Π΅Π½ΠΈΠ²Π°Ρ‚ΡŒ энСргии Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… ΠΊΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΉ, полоТСния ΠΈ ΠΈΠ½Ρ‚Снсивности ΡΠΏΠ΅ΠΊΡ‚Ρ€Π°Π»ΡŒΠ½Ρ‹Ρ… полос. Π—Π½Π°Ρ‡ΠΈΡ‚Π΅Π»ΡŒΠ½ΡƒΡŽ Ρ€ΠΎΠ»ΡŒ Π² ΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΌ ΠΌΠΎΠ΄Π΅Π»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠΈ Π·Π°Π½ΠΈΠΌΠ°ΡŽΡ‚ ΠΊΠΎΠΌΠ±ΠΈΠ½ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Π΅ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹ ΠΊΠ²Π°Π½Ρ‚ΠΎΠ²ΠΎΠΉ ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»ΡΡ€Π½ΠΎΠΉ ΠΌΠ΅Ρ…Π°Π½ΠΈΠΊΠΈ (КМ/ММ), ΡΠΎΡ‡Π΅Ρ‚Π°ΡŽΡ‰ΠΈΠ΅ Π² ΡΠ΅Π±Π΅ Ρ‚ΠΎΡ‡Π½ΠΎΡΡ‚ΡŒ ΠΊΠ²Π°Π½Ρ‚ΠΎΠ²Ρ‹Ρ… ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠ², Π½Π΅ΠΎΠ±Ρ…ΠΎΠ΄ΠΈΠΌΡƒΡŽ для описания химичСских Ρ€Π΅Π°ΠΊΡ†ΠΈΠΉ Π² ΡΠΈΡΡ‚Π΅ΠΌΠ΅, ΠΈ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡ‚ΠΈ молСкулярно-мСханичСских ΠΏΠΎΠ΄Ρ…ΠΎΠ΄ΠΎΠ² ΠΏΡ€ΠΈ ΠΌΠΎΠ΄Π΅Π»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠΈ систСм, состоящих ΠΈΠ· Π΄Π΅ΡΡΡ‚ΠΊΠΎΠ² тысяч Π°Ρ‚ΠΎΠΌΠΎΠ². Π Π°Π·Ρ€Π°Π±ΠΎΡ‚ΠΊΠ° Π½ΠΎΠ²Ρ‹Ρ… эффСктивных Π°Π»Π³ΠΎΡ€ΠΈΡ‚ΠΌΠΎΠ² ΠΌΠ΅Ρ‚ΠΎΠ΄Π° КМ/ММ, ΠΎΡ€ΠΈΠ΅Π½Ρ‚ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Ρ… Π½Π° ΡΠΎΠ²Ρ€Π΅ΠΌΠ΅Π½Π½Ρ‹Π΅ ΡΡƒΠΏΠ΅Ρ€ΠΊΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€Ρ‹, прСдставляСт Π°ΠΊΡ‚ΡƒΠ°Π»ΡŒΠ½ΡƒΡŽ Π·Π°Π΄Π°Ρ‡Ρƒ Π²Ρ‹Ρ‡ΠΈΡΠ»ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠΉ ΠΈ ΠΊΠ²Π°Π½Ρ‚ΠΎΠ²ΠΎΠΉ Ρ…ΠΈΠΌΠΈΠΈ.

ОсновноС Π²Π½ΠΈΠΌΠ°Π½ΠΈΠ΅ Π² Π΄ΠΈΡΡΠ΅Ρ€Ρ‚Π°Ρ†ΠΈΠΎΠ½Π½ΠΎΠΉ Ρ€Π°Π±ΠΎΡ‚Π΅ ΡƒΠ΄Π΅Π»Π΅Π½ΠΎ Π½ΠΎΠ²ΠΎΠΉ Ρ€Π΅Π°Π»ΠΈΠ·Π°Ρ†ΠΈΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΈΠΊΠΈ КМ/ММ с ΠΊΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΎΠ½Π½ΠΎ-ΠΏΠΎΠ΄Π²ΠΈΠΆΠ½Ρ‹ΠΌΠΈ эффСктивными Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚Π°ΠΌΠΈ ΠΈ Π΅Π΅ ΠΏΡ€ΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡŽ ΠΊ ΠΊΠΎΠ½ΠΊΡ€Π΅Ρ‚Π½Ρ‹ΠΌ Π·Π°Π΄Π°Ρ‡Π°ΠΌ модСлирования химичСских ΠΏΡ€Π΅Π²Ρ€Π°Ρ‰Π΅Π½ΠΈΠΉ, Π²ΠΊΠ»ΡŽΡ‡Π°Ρ:

β€’ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ Π² Ρ€Π°ΡΡ‚Π²ΠΎΡ€Π°Ρ… — ΠΌΠΎΠ΄Π΅Π»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ Π³ΠΈΠ΄Ρ€ΠΎΠ»ΠΈΠ·Π° цикличСского гуанозинмонофосфата Π² Π²ΠΎΠ΄Π΅,.

β€’ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π°Ρ‚ΠΈΠ²Π½Ρ‹Π΅ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ — расщСплСниС Π½Π΅ΠΉΡ€ΠΎΠΌΠ΅Π΄ΠΈΠ°Ρ‚ΠΎΡ€Π° Π°Ρ†Π΅Ρ‚ΠΈΠ»Ρ…ΠΎΠ»ΠΈΠ½Π° Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ΠΎΠΌ ацСтилхолинэстСразой,.

β€’ Ρ„ΠΎΡ‚ΠΎΡ€Π΅Π°ΠΊΡ†ΠΈΠΈ Π² Π±Π΅Π»ΠΊΠ°Ρ… — дСкарбоксилированиС Π·Π΅Π»Π΅Π½ΠΎΠ³ΠΎ флуорСсцСнтного Π±Π΅Π»ΠΊΠ°.

КаТдая ΠΈΠ· Ρ€Π°ΡΡΠΌΠΎΡ‚Ρ€Π΅Π½Π½Ρ‹Ρ… систСм прСдставляСт интСрСс для ΡΠΎΠΎΡ‚Π²Π΅Ρ‚ΡΡ‚Π²ΡƒΡŽΡ‰Π΅ΠΉ области Π±ΠΈΠΎΡ„ΠΈΠ·ΠΈΠΊΠΈ (Π±ΠΈΠΎΡ…ΠΈΠΌΠΈΠΈ), Π½ΠΎ Π΄Π»Ρ Ρ†Π΅Π»Π΅ΠΉ Π΄Π°Π½Π½ΠΎΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹ Ρ‚Π°ΠΊΠΆΠ΅ Π²Π°ΠΆΠ½ΠΎ Π±Ρ‹Π»ΠΎ ΡƒΡΡ‚Π°Π½ΠΎΠ²ΠΈΡ‚ΡŒ, насколько эффСктивно ΠΏΡ€ΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π΄Π°Π½Π½ΠΎΠΉ Ρ€Π΅Π°Π»ΠΈΠ·Π°Ρ†ΠΈΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° КМ/ММ. Π‘ ΡΡ‚ΠΎΠΉ Ρ†Π΅Π»ΡŒΡŽ Π² Ρ€ΡΠ΄Π΅ ΠΏΡ€ΠΈΠΌΠ΅Ρ€ΠΎΠ² ΠΏΡ€ΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΎΡΡŒ сравнСниС Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚ΠΎΠ² Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… Π²Π°Ρ€ΠΈΠ°Π½Ρ‚ΠΎΠ² КМ/ММ. Π’ΠΎ Π²ΡΠ΅Ρ… случаях расчСты Π²Ρ‹ΠΏΠΎΠ»Π½ΡΠ»ΠΈΡΡŒ Π½Π° ΡΡƒΠΏΠ΅Ρ€ΠΊΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€Π½Ρ‹Ρ… рСсурсах ΠœΠ“Π£ ΠΈΠΌ. Πœ. Π’. Ломоносова ΠΈΠ»ΠΈ Российской Π°ΠΊΠ°Π΄Π΅ΠΌΠΈΠΈ Π½Π°ΡƒΠΊ.

ЦСль Ρ€Π°Π±ΠΎΡ‚Ρ‹: Π Π°Π·Π²ΠΈΡ‚ΠΈΠ΅ Π°Π»Π³ΠΎΡ€ΠΈΡ‚ΠΌΠΎΠ² ΠΊΠΎΠΌΠ±ΠΈΠ½ΠΈΡ€ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° ΠΊΠ²Π°Π½Ρ‚ΠΎΠ²ΠΎΠΉ ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»ΡΡ€Π½ΠΎΠΉ ΠΌΠ΅Ρ…Π°Π½ΠΈΠΊΠΈ (КМ/ММ), ΠΎΡ€ΠΈΠ΅Π½Ρ‚ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹Ρ… Π½Π° ΡΡƒΠΏΠ΅Ρ€ΠΊΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€Ρ‹, ΠΈ Π΅Π³ΠΎ ΠΏΡ€ΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ для прогнозирования ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΠΎΠ² Ρ€Π΅Π°ΠΊΡ†ΠΈΠΉ, проходящих Π² Π±Π΅Π»ΠΊΠ°Ρ… ΠΈ Ρ€Π°ΡΡ‚Π²ΠΎΡ€Π°Ρ…. Π’ ΡΠΎΠΎΡ‚вСтствии с ΠΏΠΎΡΡ‚Π°Π²Π»Π΅Π½Π½ΠΎΠΉ Ρ†Π΅Π»ΡŒΡŽ Ρ€Π΅ΡˆΠ°Π»ΠΈΡΡŒ ΡΠ»Π΅Π΄ΡƒΡŽΡ‰ΠΈΠ΅ Π·Π°Π΄Π°Ρ‡ΠΈ:

1. РСализация ΠΌΠ΅Ρ‚ΠΎΠ΄Π° КМ/ММ Π² Π²Π°Ρ€ΠΈΠ°Π½Ρ‚Π΅ ΠΊΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΎΠ½Π½ΠΎ-ΠΏΠΎΠ΄Π²ΠΈΠΆΠ½Ρ‹Ρ… эффСктивных Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚ΠΎΠ² Π² ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌΠ½ΠΎΠΌ ΠΏΠ°ΠΊΠ΅Ρ‚Π΅ GAMESS (US).

2. ИсслСдованиС ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΠ° Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ Π³ΠΈΠ΄Ρ€ΠΎΠ»ΠΈΠ·Π° цикличСского гуанозинмонофосфата Π² Π²ΠΎΠ΄Π½ΠΎΠΌ растворС двумя Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹ΠΌΠΈ Π²Π°Ρ€ΠΈΠ°Π½Ρ‚Π°ΠΌΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° КМ/ММ.

3. ДСтализация ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΠ° расщСплСния Π°Ρ†Π΅Ρ‚ΠΈΠ»Ρ…ΠΎΠ»ΠΈΠ½Π° Π² Π°ΠΊΡ‚ΠΈΠ²Π½ΠΎΠΌ Ρ†Π΅Π½Ρ‚Ρ€Π΅ ацСтилхолинэстСразы двумя Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹ΠΌΠΈ Π²Π°Ρ€ΠΈΠ°Π½Ρ‚Π°ΠΌΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° КМ/ММ.

4. ИсслСдованиС Ρ„ΠΎΡ‚ΠΎΡ€Π΅Π°ΠΊΡ†ΠΈΠΈ дСкарбоксилирования Π·Π΅Π»Ρ‘Π½ΠΎΠ³ΠΎ флуорСсцСнтного Π±Π΅Π»ΠΊΠ°.

Научная Π½ΠΎΠ²ΠΈΠ·Π½Π° Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚ΠΎΠ²:

1. Показано, Ρ‡Ρ‚ΠΎ Π½ΠΎΠ²Ρ‹ΠΉ Π²Π°Ρ€ΠΈΠ°Π½Ρ‚ ΠΊΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€Π½ΠΎΠΉ ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌΡ‹ ΠΌΠ΅Ρ‚ΠΎΠ΄Π° КМ/ММ с ΠΊΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΎΠ½Π½ΠΎ-ΠΏΠΎΠ΄Π²ΠΈΠΆΠ½Ρ‹ΠΌΠΈ Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚Π°ΠΌΠΈ, Ρ€Π΅Π°Π»ΠΈΠ·ΠΎΠ²Π°Π½Π½Ρ‹ΠΉ Π² ΠΏΠ°ΠΊΠ΅Ρ‚Π΅ GAMESS (US), дСмонстрируСт Π²Ρ‹ΡΠΎΠΊΡƒΡŽ ΡΡ„Ρ„Π΅ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒ ΠΏΡ€ΠΈ ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ расчётов с ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΡƒΠΏΠ΅Ρ€ΠΊΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€ΠΎΠ².

2. УстановлСно, Ρ‡Ρ‚ΠΎ рСакция Π³ΠΈΠ΄Ρ€ΠΎΠ»ΠΈΠ·Π° цикличСского гуанозинмонофосфата Π² Π²ΠΎΠ΄Π½ΠΎΠΌ растворС ΠΏΡ€ΠΎΡ…ΠΎΠ΄ΠΈΡ‚ ΠΏΠΎ Π°ΡΡΠΎΡ†ΠΈΠ°Ρ‚ΠΈΠ²Π½ΠΎΠΌΡƒ ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΡƒ Ρ‡Π΅Ρ€Π΅Π· ΠΈΠ½Ρ‚Π΅Ρ€ΠΌΠ΅Π΄ΠΈΠ°Ρ‚ с ΠΏΠ΅Π½Ρ‚Π°ΠΊΠΎΠΎΡ€Π΄ΠΈΠ½ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹ΠΌ фосфором.

3. ΠŸΠΎΠ΄Ρ‚Π²Π΅Ρ€ΠΆΠ΄Π΅Π½Π° Π³ΠΈΠΏΠΎΡ‚Π΅Π·Π° ΠΎ ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΠΈ тСтраэдричСского ΠΈΠ½Ρ‚Π΅Ρ€ΠΌΠ΅Π΄ΠΈΠ°Ρ‚Π° стадии ацилирования Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ Π³ΠΈΡ€ΠΎΠ»ΠΈΠ·Π° Π°Ρ†Π΅Ρ‚ΠΈΠ»Ρ…ΠΎΠ»ΠΈΠ½Π° Π² Π°ΠΊΡ‚ΠΈΠ²Π½ΠΎΠΌ Ρ†Π΅Π½Ρ‚Ρ€Π΅ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π° ацСтилхолинэстСразы.

4. Показано, Ρ‡Ρ‚ΠΎ ΡΠΊΠΎΡ€ΠΎΡΡ‚ΡŒ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ дСкарбоксилирования Π·Π΅Π»Ρ‘Π½ΠΎΠ³ΠΎ флуорСсцСнтного Π±Π΅Π»ΠΊΠ° зависит ΠΎΡ‚ Π΄Π»ΠΈΠ½Ρ‹ Π²ΠΎΠ»Π½Ρ‹ ΠΎΠ±Π»ΡƒΡ‡Π°ΡŽΡ‰Π΅Π³ΠΎ свСта, ΠΈ Ρ€Π΅Π°ΠΊΡ†ΠΈΡ ΠΌΠΎΠΆΠ΅Ρ‚ ΠΏΡ€ΠΎΠΈΡΡ…ΠΎΠ΄ΠΈΡ‚ΡŒ ΠΊΠ°ΠΊ ΠΏΠΎ ΠΎΠ΄Π½ΠΎΡ„ΠΎΡ‚ΠΎΠ½Π½ΠΎΠΌΡƒ, Ρ‚Π°ΠΊ ΠΈ ΠΏΠΎ Π΄Π²ΡƒΡ…Ρ„ΠΎΡ‚ΠΎΠ½Π½ΠΎΠΌΡƒ ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΡƒ.

Π›ΠΈΡ‡Π½Ρ‹ΠΉ Π²ΠΊΠ»Π°Π΄ диссСртанта Π·Π°ΠΊΠ»ΡŽΡ‡Π°Π΅Ρ‚ΡΡ Π² ΡΠ±ΠΎΡ€Π΅ ΠΈ Π°Π½Π°Π»ΠΈΠ·Π΅ Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Π½Ρ‹Ρ… Π΄Π°Π½Π½Ρ‹Ρ…, постановкС Π·Π°Π΄Π°Ρ‡, Ρ€Π°Π·Ρ€Π°Π±ΠΎΡ‚ΠΊΠ΅ ΠΏΡƒΡ‚Π΅ΠΉ Ρ€Π΅ΡˆΠ΅Π½ΠΈΡ поставлСнных Π·Π°Π΄Π°Ρ‡, рСализация Π°Π»Π³ΠΎΡ€ΠΈΡ‚ΠΌΠΎΠ² ΠΌΠ΅Ρ‚ΠΎΠ΄Π° ΠΊΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΎΠ½Π½ΠΎ-ΠΏΠΎΠ΄Π²ΠΈΠΆΠ½Ρ‹Ρ… эффСктивных Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚ΠΎΠ² Π² ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌΠ½ΠΎΠΌ ΠΏΠ°ΠΊΠ΅Ρ‚Π΅ ΠžΠΠœΠ•88(ΠΈ8), ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ вычислСний ΠΌΠ΅Ρ‚ΠΎΠ΄Π°ΠΌΠΈ ΠΊΠ²Π°Π½Ρ‚ΠΎΠ²ΠΎΠΉ Ρ…ΠΈΠΌΠΈΠΈ, ΠΊΠΎΠΌΠ±ΠΈΠ½ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹ΠΌΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Π°ΠΌΠΈ ΠΊΠ²Π°Π½Ρ‚ΠΎΠ²ΠΎΠΉ ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»ΡΡ€Π½ΠΎΠΉ ΠΌΠ΅Ρ…Π°Π½ΠΈΠΊΠΈ, ΠΈΠ½Ρ‚Π΅Ρ€ΠΏΡ€Π΅Ρ‚Π°Ρ†ΠΈΠΈ Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚ΠΎΠ², ΠΏΠΎΠ΄Π³ΠΎΡ‚ΠΎΠ²ΠΊΠ΅ ΠΏΡƒΠ±Π»ΠΈΠΊΠ°Ρ†ΠΈΠΉ ΠΈ Π΄ΠΎΠΊΠ»Π°Π΄ΠΎΠ² ΠΏΠΎ Ρ‚Π΅ΠΌΠ΅ диссСртационной Ρ€Π°Π±ΠΎΡ‚Ρ‹.

Научная ΠΈ ΠΏΡ€Π°ΠΊΡ‚ичСская Π·Π½Π°Ρ‡ΠΈΠΌΠΎΡΡ‚ΡŒ Π΄Π°Π½Π½ΠΎΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹ Π·Π°ΠΊΠ»ΡŽΡ‡Π°Π΅Ρ‚ΡΡ Π² Ρ‚ΠΎΠΌ, Ρ‡Ρ‚ΠΎ ΠΏΠΎΠ»ΡƒΡ‡Π΅Π½Π½Ρ‹Π΅ Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡŽΡ‚ Π΄Π΅Ρ‚Π°Π»ΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΡ‹ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π°Ρ‚ΠΈΠ²Π½Ρ‹Ρ… ΠΈ Ρ„отохимичСских Ρ€Π΅Π°ΠΊΡ†ΠΈΠΉ для ΡˆΠΈΡ€ΠΎΠΊΠΎΠ³ΠΎ класса Π±Π΅Π»ΠΊΠΎΠ². Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ Π΄Π°Π½Π½ΠΎΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹ ΠΌΠΎΠ³ΡƒΡ‚ Π±Ρ‹Ρ‚ΡŒ ΠΏΡ€ΠΈΠΌΠ΅Π½Π΅Π½Ρ‹, Π² Ρ‡Π°ΡΡ‚ности, для прогнозирования свойств Π½ΠΎΠ²Ρ‹Ρ… пСрспСктивных Π±ΠΈΠΎΠΌΠ°Ρ€ΠΊΠ΅Ρ€ΠΎΠ² Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ флуорСсцСнтных Π±Π΅Π»ΠΊΠΎΠ², Π½ΠΎΠ²Ρ‹Ρ… ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π»ΡŒΠ½Ρ‹Ρ… ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€ΠΎΠ² ваТнСйшСго Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π° Π²Ρ‹ΡΡˆΠ΅ΠΉ Π½Π΅Ρ€Π²Π½ΠΎΠΉ Π΄Π΅ΡΡ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ — ацСтилхолинэстСразы.

Апробация Ρ€Π°Π±ΠΎΡ‚Ρ‹ ΠΈ ΠΏΡƒΠ±Π»ΠΈΠΊΠ°Ρ†ΠΈΠΈ. ΠœΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»Ρ‹ диссСртации Π±Ρ‹Π»ΠΈ прСдставлСны Π½Π° ΠΌΠ΅ΠΆΠ΄ΡƒΠ½Π°Ρ€ΠΎΠ΄Π½Ρ‹Ρ… конфСрСнциях «Π›ΠΎΠΌΠΎΠ½ΠΎΡΠΎΠ²» (Москва 2009 ΠΈ 2011), 7-ΠΉ ВсСроссийской ΠΊΠΎΠ½Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΠΈ «ΠœΠΎΠ»Π΅ΠΊΡƒΠ»ΡΡ€Π½ΠΎΠ΅ ΠΌΠΎΠ΄Π΅Π»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅» (Москва 2011), IX ΠΈ X Π΅ΠΆΠ΅Π³ΠΎΠ΄Π½Ρ‹Ρ… ΠΌΠ΅ΠΆΠ΄ΡƒΠ½Π°Ρ€ΠΎΠ΄Π½Ρ‹Ρ… ΠΌΠΎΠ»ΠΎΠ΄Π΅ΠΆΠ½Ρ‹Ρ… конфСрСнциях «Π‘иохимичСская Ρ„ΠΈΠ·ΠΈΠΊΠ°» Π˜Π‘Π₯Π€ РАН-Π’Π£Π—Ρ‹ (Москва 2009, 2010), Π‘ΠΈΠΌΠΏΠΎΠ·ΠΈΡƒΠΌΠ°Ρ… «Π‘оврСмСнная химичСская Ρ„ΠΈΠ·ΠΈΠΊΠ°» (ВуапсС 2010 ΠΈ 2011), 5-ΠΉ ΠΌΠ΅ΠΆΠ΄ΡƒΠ½Π°Ρ€ΠΎΠ΄Π½ΠΎΠΉ ΠΊΠΎΠ½Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΠΈ «ΠŸΠ°Ρ€Π°Π»Π»Π΅Π»ΡŒΠ½Ρ‹Π΅ Π²Ρ‹Ρ‡ΠΈΡΠ»ΠΈΡ‚Π΅Π»ΡŒΠ½Ρ‹Π΅ Ρ‚Π΅Ρ…Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ (ΠŸΠ°Π’Π’)» (Москва 2011), 26-ΠΉ Π·ΠΈΠΌΠ½Π΅ΠΉ школС тСорСтичСской Ρ…ΠΈΠΌΠΈΠΈ.

Ѐинляндия 2010), 19-ΠΉ ΠΌΠ΅ΠΆΠ΄ΡƒΠ½Π°Ρ€ΠΎΠ΄Π½ΠΎΠΉ ΠΊΠΎΠ½Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΠΈ «ΠΠΎΠ²Ρ‹Π΅ Π³ΠΎΡ€ΠΈΠ·ΠΎΠ½Ρ‚Ρ‹ Π² ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡΡ… Π²ΠΎΠ΄ΠΎΡ€ΠΎΠ΄Π½Ρ‹Ρ… связСй» (ГСрмания 2011).

Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ ΠΎΠΏΡƒΠ±Π»ΠΈΠΊΠΎΠ²Π°Π½Ρ‹ Π² 11 ΠΏΠ΅Ρ‡Π°Ρ‚Π½Ρ‹Ρ… изданиях, Π² Ρ‚ΠΎΠΌ числС Π² 6 ΡΡ‚Π°Ρ‚ΡŒΡΡ… Π² Ρ€Π΅Ρ†Π΅Π½Π·ΠΈΡ€ΡƒΠ΅ΠΌΡ‹Ρ… Π½Π°ΡƒΡ‡Π½Ρ‹Ρ… ΠΆΡƒΡ€Π½Π°Π»Π°Ρ…, входящих Π² ΠΏΠ΅Ρ€Π΅Ρ‡Π΅Π½ΡŒ ΠΆΡƒΡ€Π½Π°Π»ΠΎΠ² Π’ΠΠš Π Π€ ΠΈ Π² 5 тСзисах Π΄ΠΎΠΊΠ»Π°Π΄ΠΎΠ² Π½Π° ΠΊΠΎΠ½Ρ„СрСнциях.

Π’Ρ‹Π²ΠΎΠ΄Ρ‹.

1. Π‘ ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π½ΠΎΠ²ΠΎΠΉ Ρ€Π΅Π°Π»ΠΈΠ·Π°Ρ†ΠΈΠΈ Π°Π»Π³ΠΎΡ€ΠΈΡ‚ΠΌΠΎΠ² ΠΌΠ΅Ρ‚ΠΎΠ΄Π° КМ/ММ Π² Π²Π°Ρ€ΠΈΠ°Π½Ρ‚Π΅ ΠΊΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΎΠ½Π½ΠΎ-ΠΏΠΎΠ΄Π²ΠΈΠΆΠ½Ρ‹Ρ… Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚ΠΎΠ² Π² ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌΠ½ΠΎΠΌ ΠΏΠ°ΠΊΠ΅Ρ‚Π΅ GAMES S (US) ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½Ρ‹ расчСты свойств ряда биомолСкулярных систСм ΠΈ ΠΏΠΎΠΊΠ°Π·Π°Π½Π° ΡΡ„Ρ„Π΅ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒ Π΄Π°Π½Π½ΠΎΠΉ Ρ€Π΅Π°Π»ΠΈΠ·Π°Ρ†ΠΈΠΈ Π½Π° ΡΠΎΠ²Ρ€Π΅ΠΌΠ΅Π½Π½Ρ‹Ρ… ΡΡƒΠΏΠ΅Ρ€ΠΊΠΎΠΌΠΏΡŒΡŽΡ‚Π΅Ρ€Π°Ρ….

2. Π‘ ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π΄Π²ΡƒΡ… Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… Π²Π°Ρ€ΠΈΠ°Π½Ρ‚ΠΎΠ² ΠΌΠ΅Ρ‚ΠΎΠ΄Π° КМ/ММ (ΠΊΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ°Ρ†ΠΈΠΎΠ½Π½ΠΎ-ΠΏΠΎΠ΄Π²ΠΈΠΆΠ½Ρ‹Ρ… эффСктивных Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚ΠΎΠ² ΠΈ Π²Π½Π΅Π΄Ρ€Ρ‘Π½Π½ΠΎΠ³ΠΎ кластСра) установлСно, Ρ‡Ρ‚ΠΎ рСакция Π³ΠΈΠ΄Ρ€ΠΎΠ»ΠΈΠ·Π° цикличСского гуанозинмонофосфата Π² Π²ΠΎΠ΄Π½ΠΎΠΌ растворС ΠΏΡ€ΠΎΡ‚Π΅ΠΊΠ°Π΅Ρ‚ ΠΏΠΎ Π°ΡΡΠΎΡ†ΠΈΠ°Ρ‚ΠΈΠ²Π½ΠΎΠΌΡƒ ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΡƒ с ΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΈΠ½Ρ‚Π΅Ρ€ΠΌΠ΅Π΄ΠΈΠ°Ρ‚Π° с ΠΏΠ΅Π½Ρ‚Π°ΠΊΠΎΠΎΡ€Π΄ΠΈΠ½ΠΈΡ€ΠΎΠ²Π°Π½Π½Ρ‹ΠΌ фосфором.

3. Двумя Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹ΠΌΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Π°ΠΌΠΈ КМ/ММ ΠΏΠΎΠ΄Ρ‚Π²Π΅Ρ€ΠΆΠ΄Π΅Π½Π° ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΡŒ тСтраэдричСского ΠΈΠ½Ρ‚Π΅Ρ€ΠΌΠ΅Π΄ΠΈΠ°Ρ‚Π° стадии ацилирования Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ Π³ΠΈΠ΄Ρ€ΠΎΠ»ΠΈΠ·Π° Π°Ρ†Π΅Ρ‚ΠΈΠ»Ρ…ΠΎΠ»ΠΈΠ½Π° Π² Π°ΠΊΡ‚ΠΈΠ²Π½ΠΎΠΌ Ρ†Π΅Π½Ρ‚Ρ€Π΅ ацСтилхолинэстСразы. ΠŸΠΎΠ΄Ρ‚Π²Π΅Ρ€ΠΆΠ΄Π΅Π½ΠΎ, Ρ‡Ρ‚ΠΎ данная рСакция ΠΏΡ€ΠΎΡ…ΠΎΠ΄ΠΈΡ‚ ΠΏΠΎ ΠΎΠ΄Π½ΠΎΠΏΡ€ΠΎΡ‚ΠΎΠ½Π½ΠΎΠΌΡƒ ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΡƒ.

4. ΠŸΡ€Π΅Π΄Π»ΠΎΠΆΠ΅Π½Ρ‹ сцСнарии Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ дСкарбоксилирования Π·Π΅Π»Ρ‘Π½ΠΎΠ³ΠΎ флуорСсцСнтного Π±Π΅Π»ΠΊΠ° с ΡƒΡ‡Π΅Ρ‚ΠΎΠΌ пСрСносом элСктрона с Π°Π½ΠΈΠΎΠ½Π° Glu222 Π½Π° Ρ…Ρ€ΠΎΠΌΠΎΡ„ΠΎΡ€ с ΡƒΡ‡Π°ΡΡ‚ΠΈΠ΅ΠΌ высоко-Π»Π΅ΠΆΠ°Ρ‰ΠΈΡ… Π²ΠΎΠ·Π±ΡƒΠΆΠ΄Π΅Π½Π½Ρ‹Ρ… состояний. s.

ΠŸΠΎΠΊΠ°Π·Π°Ρ‚ΡŒ вСсь тСкст

Бписок Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Ρ‹

  1. А., М. Levitt, Theoretical studies of enzymic reactions: Dielectric, electrostatic and steric stabilization of the carbonium ion in the reaction of lysozyme. //J. Mol. Biol., 1976.103(2): p. 227−249.
  2. Warshel A., M. Karplus, Calculation of ground and excited state potential surfaces of conjugated molecules. I. Formulation and parametrization. // J. Am. Chem. Soc., 1972. 94(16): p. 5612−5625.
  3. Field M.J., P.A. Bash, M. Karplus, A combined quantum mechanical and molecular mechanical potential for molecular dynamics simulations. // J. Comput. Chem., 1990.11(6): p. 700−733.
  4. Gao J., Hybrid Quantum and Molecular Mechanical Simulations:? An Alternative Avenue to Solvent Effects in Organic Chemistry. // Acc. Chem. Res., 1996. 29(6): p. 298−305.
  5. Gao J., Methods and Applications of Combined Quantum Mechanical and Molecular Mechanical Potentials, in Reviews in Computational Chemistry 2007, John Wiley & Sons, Inc. p. 119−185.
  6. Cunningham M.A., P.A. Bash, Computational enzymology. // Biochimie, 1997. 79(11): p. 687−689.
  7. Π’., Π’. Clark, Some biological applications of semiempirical MO theory. // Perspect. Drug Discovery Des., 1998. 9−11(0): p. 131−159.
  8. Hillier I.H., Chemical reactivity studied by hybrid QM/MM methods. // THEOCHEM, 1999. 463(1−2): p. 45−52.
  9. Sherwood P., Hybrid quantum mechanics/molecular mechanics approaches. // Modern methods and algorithms of quantum chemistry, 2000.3: p. 257−277.
  10. MacKerell Jr A.D., Atomistic models and force fields. // Computational biochemistry and biophysics, 2001: p. 7−38.
  11. Ponder J.W., D.A. Case, Force fields for protein simulations. // Advances in protein chemistry, 2003. 66: p. 27−85.-s
  12. Senn H., W. Thiel, QM/MM Methods for Biological Systems
  13. Atomistic Approaches in Modern Biology, M. Reiher, Editor 2007, Springer Berlin / Heidelberg, p. 173−290.
  14. Mackerell A.D., Empirical force fields for biological macromolecules: Overview and issues. //J. Comput. Chem., 2004. 25(13): p. 1584−1604.
  15. Maseras F., K. Morokuma, IMOMM: A new integrated ab initio + molecular mechanics geometry optimization scheme of equilibrium structures and transition states. //J. Comput. Chem., 1995.16(9): p. 1170−1179.
  16. Dapprich S., I. Komaromi, K.S. Byun, K. Morokuma, M.J. Frisch, A new ONIOM implementation in Gaussian98. Part I. The calculation of energies, gradients, vibrational frequencies and electric field derivatives. //THEOCHEM, 1999. 461−462(0): p. 1−21.
  17. Froese R.D.J., K. Morokuma, Hybrid methods. // Encyclopedia of computational chemistry, 1998.
  18. Komaromi I., L. Muszbek, Application of the IMOMM (integrated molecular orbital molecular mechanics) method for biopolymers. // Frontiers of multifunctional nanosystems. NATO science series II: Mathematics, physics and chemistry, 2002. 57: p. 17−28.
  19. Vreven T., K.S. Byun, I. Komaromi, S. Dapprich, J.A. Montgomery, K. Morokuma, M.J. Frisch, Combining Quantum Mechanics Methods with Molecular Mechanics Methods in ONIOM. //J. Chem. Theory Comput., 2006. 2(3): p. 815 826.
  20. Vreven T., K. Morokuma, Investigation of the S 0- S 1 excitation in bacteriorhodopsin with the ONIOM (MO: MM) hybrid method. // Theor. Chem. Acc., 2003.109(3): p. 125−132.
  21. Bakowies D., W. Thiel, Hybrid Models for Combined Quantum Mechanical and Molecular Mechanical Approaches. //J. Phys. Chem., 1996. 100(25): p. 1 058 010 594.
  22. Antes I., W. Thiel. On the treatment of link atoms in hybrid methods. 1998. ACS Publications.
  23. Rick S. W., S.J. Stuart, Potentials and Algorithms for Incorporating Polarizability in Computer Simulations, in Reviews in Computational Chemistry, 2003, John Wiley & Sons, Inc. p. 89−146.
  24. Yu H., W.F. van Gunsteren, Accounting for polarization in molecular simulation. //Comput. Phys. Commun., 2005.172(2): p. 69−85.
  25. Stern H.A., F. Rittner, BJ. Berne, R.A. Friesner, Combined fluctuating charge and polarizable dipole models: Application to a five-site water potential function. //J. Chem. Phys., 2001.115(5): p. 2237−2251.
  26. Grossfield A., P. Ren, J.W. Ponder, Ion Solvation Thermodynamics from Simulation with a Polarizable Force Field. // J. Am. Chem. Soc., 2003. 125(50): p. 15 671−15 682.
  27. Lamoureux G., J.A.D. MacKerell, B. Roux, A simple polarizable model of water based on classical Drude oscillators. //J. Chem. Phys., 2003. 119(10): p. 51 855 197.
  28. Lamoureux G., B. Roux, Modeling induced polarization with classical Drude oscillators: Theory and molecular dynamics simulation algorithm. // J. Chem. Phys., 2003.119(6): p. 3025−3039.
  29. Ren P., J.W. Ponder, Polarizable Atomic Multipole Water Model for Molecular Mechanics Simulation. //J. Phys. Chem. B, 2003.107(24): p. 5933−5947.
  30. Yu H., T. Hansson, W.F. van Gunsteren, Development of a simple, self-consistent polarizable model for liquid water. // J. Chem. Phys., 2003.118(1): p. 221−234.
  31. Yu H., W.F. van Gunsteren, Charge-on-springpolarizable water models revisited: From water clusters to liquid water to ice. // J. Chem. Phys., 2004. 121(19): p. 9549−9564.
  32. Anisimov V.M., G. Lamoureux, I.V. Vorobyov, N. Huang, B. Roux, A.D. MacKerell, Determination of Electrostatic Parameters for a Polarizable Force Field Based on the Classical Drude Oscillator. //J. Chem. Theory Comput., 2004. 1(1): p. 153−168.
  33. Patel S., A.D. Mackerell, C.L. Brooks, CHARMM fluctuating charge force field for proteins: II Protein/solvent properties from molecular dynamics simulationsusing a nonadditive electrostatic model // J. Comput. Chem., 2004. 25(12): p. 1504−1514.
  34. Vorobyov I.V., V.M. Anisimov, A.D. MacKerell, Polarizable Empirical Force Field for Alkanes Based on the Classical Drude Oscillator Model. // J. Phys. Chem. B, 2005.109(40): p. 18 988−18 999.
  35. Wang J., P. Cieplak, P.A. Kollman, How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? //J. Comput. Chem., 2000. 21(12): p. 1049−1074.
  36. Wang Z.-X., W. Zhang, C. Wu, H. Lei, P. Cieplak, Y. Duan, Strike a balance: Optimization of backbone torsion parameters of AMBER polarizable force field for simulations ofproteins and peptides. // J. Comput. Chem., 2006. 27(6): p. 781 790.
  37. Banks J.L., G.A. Kaminski, R. Zhou, D.T. Mainz, B.J. Berne, R.A. Friesner, Parametrizing a polarizable force field from ab initio data. I. The fluctuating point charge model. //J. Chem. Phys., 1999.110(2): p. 741−754.
  38. Stern H.A., G.A. Kaminski, J.L. Banks, R. Zhou, B.J. Berne, R.A. Friesner, Fluctuating Charge, Polarizable Dipole, and Combined Models:? Parameterization from ab Initio Quantum Chemistry. // J. Phys. Chem. B, 1999. 103(22): p. 4730−4737.
  39. Kaminski G.A., H.A. Stern, B.J. Berne, R.A. Friesner, Development of an Accurate and Robust Polarizable Molecular Mechanics Force Field from ab Initio Quantum Chemistry. //J. Phys. Chem. A, 2003.108(4): p. 621−627.
  40. Ren P., J.W. Ponder, Consistent treatment of inter- and intramolecular polarization in molecular mechanics calculations. // J. Comput. Chem., 2002. 23(16): p. 1497−1506.
  41. Thompson M.A., G.K. Schenter, Excited States of the Bacteriochlorophyll b Dimer of Rhodopseudomonas viridis: A QM/MM Study of the Photosynthetic
  42. Reaction Center That Includes MM Polarization. //J. Phys. Chem., 1995. 99(17): p. 6374−6386.
  43. Nam K., J. Gao, D.M. York, An Efficient Linear-Scaling Ewald Method for LongRange Electrostatic Interactions in Combined QM/MM Calculations. // J. Chem. Theory Comput., 2004.1(1): p. 2−13.
  44. Dinner A.R., X. Lopez, M. Karplus, A charge-scaling method to treat solvent in QM/MM simulations. //Theor. Chem. Acc., 2003.109(3): p. 118−124.
  45. Gregersen B.A., D.M. York, Variational Electrostatic Projection (VEP) Methods for Efficient Modeling of the Macromolecular Electrostatic and Solvation Environment in Activated Dynamics Simulations. // J. Phys. Chem. B, 2004. 109(1): p. 536−556.
  46. Gregersen B.A., D.M. York, A charge-scaling implementation of the variational electrostatic projection method. // J. Comput. Chem., 2006. 27(1): p. 103−115.
  47. Schaefer P., D. Riccardi, Q. Cui, Reliable treatment of electrostatics in combined QM/MM simulation of macromolecules. // J. Chem. Phys., 2005. 123(1): p. 14 905−14.
  48. Beglov D., B. Roux, Finite representation of an infinite bulk system: Solvent boundary potential for computer simulations. //J. Chem. Phys., 1994. 100(12): p. 9050−9063.
  49. King G., A. Warshel, A surface constrained all-atom solvent model for effective simulations of polar solutions. //J. Chem. Phys., 1989. 91(6): p. 3647−3661.
  50. Im W., S. Berneche, B. Roux, Generalized solvent boundary potential for computer simulations. //J. Chem. Phys., 2001.114(7): p. 2924−2937.
  51. Riccardi D., P. Schaefer, Q. Cui, pKa Calculations in Solution and Proteins with QM/MM Free Energy Perturbation Simulations: U A Quantitative Test of QM/MM Protocols. //J. Phys. Chem. B, 2005.109(37): p. 17 715−17 733.is
  52. Konig P.H., N. Ghosh, M. Hoffmann, M. Elstner, E. Tajkhorshid, T. Frauenheim, Q. Cui, Toward Theoretical Analyis of Long-Range Proton Transfer Kinetics in Biomolecular Pumps f. //J. Phys. Chem. A, 2005.110(2): p. 548−563.
  53. Murphy R.B., D.M. Philipp, R.A. Friesner, A mixed quantum mechanics/molecular mechanics (QM/MM) method for large-scale modeling of chemistry in protein environments. // J. Comput. Chem., 2000. 21(16): p. 14 421 457.
  54. Freindorf M., Y. Shao, T.R. Furlani, J. Kong, Lennard-Jones parameters for the combined QM/MM method using the B3LYP/6−31G*/AMBER potential. // J. Comput. Chem., 2005.26(12): p. 1270−1278.
  55. Riccardi D., G. Li, Q. Cui, Importance of van der Waals Interactions in QM/MM Simulations. //J. Phys. Chem. B, 2004.108(20): p. 6467−6478.
  56. Eichinger M., P. Tavan, J. Hutter, M. Parrinello, A hybrid method for solutes in complex solvents: Density functional theory combined with empirical force fields. //J. Chem. Phys., 1999.110(21): p. 10 452−10 467.
  57. Eichler U., C.M. Kolmel, J. Sauer, Combining ab initio techniques with analytical potential functions for structure predictions of large systems: Method and application to crystalline silica polymorphs. //J. Comput. Chem., 1997. 18(4): p. 463−477.
  58. Field M.J., M. Albe, C. Bret, F. Proust-De Martin, A. Thomas, The dynamo library for molecular simulations using hybrid quantum mechanical and1. S, molecular mechanical potentials. // J. Comput. Chem., 2000. 21(12): p. 10 881 100.
  59. Lyne P.D., M. Hodoscek, M. Karplus, A Hybrid QM-MM Potential Employing Hartree-Fock or Density Functional Methods in the Quantum Region. // J. Phys. Chem. A, 1999.103(18): p. 3462−3471.
  60. Swart M., AddRemove: A new link model for use in QM/MM studies. // Int. J. Quantum Chem., 2003. 91(2): p. 177−183.
  61. Woo T.K., L. Cavallo, T. Ziegler, Implementation of the IMOMM methodology for performing combined QM/MM molecular dynamics simulations and frequency calculations. //Theor. Chem. Acc., 1998.100(5): p. 307−313.
  62. Ferre N., M. Olivucci, The amide bond: pitfalls and drawbacks of the link atom scheme. //THEOCHEM, 2003. 632(1−3): p. 71−82.
  63. Lin H., D.G. Truhlar, Redistributed Charge and Dipole Schemes for Combined Quantum Mechanical and Molecular Mechanical Calculations. // J. Phys. Chem. A, 2005.109(17): p. 3991−4004.
  64. Waszkowycz B., I.H. Hillier, N. Gensmantel, D.W. Payling, A quantum mechanical/molecular mechanical model of inhibition of the enzyme phospholipase A2. //J. Chem. Soc., Perkin Trans. 2, 1991(11): p. 1819−1832.
  65. Amara P., M.J. Field, Evaluation of an ab initio quantum mechanical/molecular mechanical hybrid-potential link-atom method. // Theor. Chem. Acc., 2003. 109(1): p. 43−52.
  66. CPMD. http://www.cpmd.org/.
  67. Antes I., W. Thiel, Adjusted Connection Atoms for Combined Quantum Mechanical and Molecular Mechanical Methods. // J. Phys. Chem. A, 1999. 103(46): p. 9290−9295.
  68. Zhang Y., Improved pseudobonds for combined ab initio quantum mechanical/molecular mechanical methods. // J. Chem. Phys., 2005. 122(2): p. 24 114−7.
  69. Zhang Y., T.-S. Lee, W. Yang, A pseudobond approach to combining quantum mechanical and molecular mechanical methods. //J. Chem. Phys., 1999. 110(1): p. 46−54.
  70. Bessac F., F. Alary, Y. Carissan, J.-L. Heully, J.-P. Daudey, R. Poteau, Effective group potentials: a powerful tool for hybrid QM/MM methods? // THEOCHEM, 2003. 632(1−3): p. 43−59.
  71. Carissan Y., F. Bessac, F. Alary, J.-L. Heully, R. Poteau, What can we do with an effective group potential? //Int. J. Quantum Chem., 2006.106(3): p. 727−733.
  72. Poteau R., I. Ortega, F. Alary, A.R. Solis, J.-C. Barthelat, J.-P. Daudey, Effective Group Potentials. 1. Method. //J. Phys. Chem. A, 2000.105(1): p. 198−205.
  73. DiLabio G.A., R.A. Wolkow, E.R. Johnson, Efficient silicon surface and cluster modeling using quantum capping potentials. // J. Chem. Phys., 2005. 122(4): p. 44 708−5.
  74. Laio A., J. VandeVondele, U. Rothlisberger, A Hamiltonian electrostatic coupling scheme for hybrid Car—Parrinello molecular dynamics simulations. // J. Chem. Phys., 2002.116(16): p. 6941−6947.
  75. Slavicek P., T.J. Martinez, Multicentered valence electron effective potentials: A solution to the link atom problem for ground and excited electronic states. // J. Chem. Phys., 2006.124(8): p. 84 107−10.
  76. Assfeld X., N. Ferre, J.L. Rivail. The Local Self-Consistent Field Principles and Applications to Combined Quantum Mechanical-Molecular Mechanical Computations on Biomacromolecular Systems. 1998. ACS Publications.
  77. Ferre N., X. Assfeld, J.-L. Rivail, Specific force field parameters determination for the hybrid ab initio QMJMMLSCF method. //J. Comput. Chem., 2002. 23(6): p.610−624.
  78. Monard G., M. Loos, V. Thery, K. Baka, J.-L. Rivail, Hybrid classical quantum force field for modeling very large molecules. // Int. J. Quantum Chem., 1996. 58(2): p. 153−159.
  79. Philipp D.M., R.A. Friesner, Mixed ab initio QM/MM modeling using frozen orbitals and tests with alanine dipeptide and tetrapeptide. // J. Comput. Chem., 1999. 20(14): p. 1468−1494.
  80. Amara P., M.J. Field, C. Alhambra, J. Gao, The generalized hybrid orbital method for combined quantum mechanical/molecular mechanical calculations: formulation and tests of the analytical derivatives. // Theor. Chem. Acc., 2000. 104(5): p. 336−343.
  81. Gao J., P. Amara, C. Alhambra, M.J. Field, A Generalized Hybrid Orbital (GHO) Method for the Treatment of Boundary Atoms in Combined QM/MM Calculations. //J. Phys. Chem. A, 1998.102(24): p. 4714−4721.
  82. Pu J., J. Gao, D.G. Truhlar, Combining Self-Consistent-Charge Density-Functional Tight-Binding (SCC-DFTB) with Molecular Mechanics by the Generalized Hybrid Orbital (GHO) Method. // J. Phys. Chem. A, 2004. 108(25): p. 5454−5463.
  83. Pu J., J. Gao, D.G. Truhlar, Generalized Hybrid Orbital Method for Combining Density Functional Theory with Molecular Mechanicals. // ChemPhysChem, 2005. 6(9): p. 1853−1865.
  84. Case D.A., T.E. Cheatham, T. Darden, H. Gohlke, R. Luo, K.M. Merz, A. Onufriev, C. Simmerling, B. Wang, R.J. Woods, The Amber biomolecular simulation programs. // J. Comput. Chem., 2005.26(16): p. 1668−1688.
  85. MacKerell Jr A.D., B. Brooks, C.L. Brooks III, L. Nilsson, B. Roux, Y. Won, M. Karplus, CHARMM: the energy function and its parameterization. // Encyclopedia of computational chemistry, 1998.
  86. Martyn F., I.J. Bush, H.J.J. Van Dam, P. Sherwood, J.M.H. Thomas, J.H. Van Lenthe, R.W.A. Havenith, J. Kendrick, The GAMESS-UK electronic structure package: algorithms, developments and applications. // Molecular Physics, 2005. 103(6−8): p. 719−747.
  87. GAUSSIAN. Available from: http://www.gaussian.com/.
  88. Kendall R.A., E. Apra, D.E. Bernholdt, E.J. Bylaska, M. Dupuis, G.I. Fann, RJ. Harrison, J. Ju, J.A. Nichols, J. Nieplocha, T.P. Straatsma, T.L. Windus, A.T.
  89. Wong, High performance computational chemistry: An overview of NWChem a distributed parallel application. // Comput. Phys. Commun., 2000. 128(1−2): p. 260−283.
  90. Colombo M.C., L. Guidoni, A. Laio, A. Magistrate, P. Maurer, S. Piana, U. Rohrig, K. Spiegel, M. Sulpizi, J. VandeVondele, Hybrid QM/MM Car-Parrinello simulations of catalytic and enzymatic reactions. // CHIMIA, 56, 2002. 1(2): p. 13−19.
  91. Laino T., F. Mohamed, A. Laio, M. Parrinello, An Efficient Real Space Multigrid QM/MM Electrostatic Coupling. //J. Chem. Theory Comput., 2005.1(6): p. 11 761 184.
  92. QMMM. Available from: http://comp.chem.umn.edu/qmmm/.
  93. Gordon M.S., M.A. Freitag, P. Bandyopadhyay, J.H. Jensen, V. Kairys, W.J. Stevens, The effective fragment potential method: a QM-based MM approach to modeling environmental effects in chemistry. // J. Phys. Chem. A, 2001. 105(2): p. 293−307.
  94. Adamovic I., M.A. Freitag, M.S. Gordon, Density functional theory based effective fragment potential method. // J. Chem. Phys., 2003.118: p. 6725−6733.
  95. Gordon M.S., L. Slipchenko, H. Li, J.H. Jensen, The effective fragment potential: A general method for predicting intermolecular interactions. // Ann. Rep. Comp. Chem., 2007.3: p. 177−193.
  96. Jensen J.H., Modeling intermolecular exchange integrals between nonorthogonal molecular orbitals. //J. Chem. Phys., 1996.104: p. 7795−7797.
  97. Jensen J.H., M.S. Gordon, An approximate formula for the intermolecular Pauli repulsion between closed shell molecules. II Application to the effective fragment potential method. //J. Chem. Phys., 1998.108: p. 4772−4783.
  98. Bash P.A., M.J. Field, M. Karplus, Free energy perturbation method for chemical reactions in the condensed phase: a dynamic approach based on a combined quantum and molecular mechanics potential. // J. Am. Chem. Soc., 1987.109(26): p. 8092−8094.
  99. Krauss M., Effective fragment potentials and spectroscopy at enzyme active sites. //Comput. Chem., 1995.19(3): p. 199−204.
  100. Wladkowski B.D., M. Krauss, W.J. Stevens, Transphosphorylation catalyzed by ribonuclease A: computational study using ab initio effective fragment potentials. //J. Am. Chem. Soc., 1995.117(42): p. 10 537−10 545.
  101. Day P.N., J.H. Jensen, M.S. Gordon, S.P. Webb, W.J. Stevens, M. Krauss, D. Garmer, H. Basch, D. Cohen, An effective fragment method for modeling solvent effects in quantum mechanical calculations. // J. Chem. Phys., 1996.105: p. 1968.
  102. Nemukhin A.V., B.L. Grigorenko, A.V. Bochenkova, I.A. Topol, S.K. Burt, A QM/MM approach with effective fragment potentials applied to the dipeptide-water structures. //THEOCHEM, 2002. 581(1−3): p. 167−175.
  103. Nemukhin A.V., B.L. Grigorenko, I.A. Topol, S.K. Burt, Flexible effective fragment QM/MM method: Validation through the challenging tests. //J. Comput. Chem., 2003.24(12): p. 1410−1420.
  104. Chen W., M.S. Gordon, The effective fragment model for solvation: Internal rotation informamide. //J. Chem. Phys., 1996.105(24): p. 11 081−11 090.
  105. Day P.N., R. Pachter, M.S. Gordon, G.N. Merrill, A study of water clusters using the effective fragment potential and Monte Carlo simulated annealing. // J. Chem. Phys., 2000.112(5): p. 2063−2073.
  106. Krauss M., S.P. Webb, Solvation and the excited states offormamide. // J. Chem. Phys., 1997.107(15): p. 5771−5775.
  107. Nemukhin A.V., I.A. Topol, B.L. Grigorenko, S.K. Burt, On the Origin of Potential Barrier for the Reaction OH- + C02 → HC03- in Water:? Studies by Using Continuum and Cluster Solvation Methods. // J. Phys. Chem. B, 2002. 106(7): p. 1734−1740.
  108. Kairys V., J.H. Jensen, QM/MM Boundaries Across Covalent Bonds:? A Frozen Localized Molecular Orbital-Based Approach for the Effective Fragment Potential Method. //J. Phys. Chem. A, 2000.104(28): p. 6656−6665.
  109. Krauss M., B.D. Wladkowski, Vanadate complex spectroscopy at the RNase A active site. //Int. J. Quantum Chem., 1998. 69(1): p. 11−19.
  110. Li H., A.W. Hains, J.E. Everts, A.D. Robertson, J.H. Jensen, The Prediction of Protein pKa’s Using QM/MM:? The pKa of Lysine 55 in Turkey Ovomucoid Third Domain. //J. Phys. Chem. B, 2002.106(13): p. 3486−3494.
  111. Roitberg A.E., S.E. Worthington, M.J. Holden, M.P. Mayhew, M. Krauss, The Electronic Spectrum of the Prephenate Dianion. An Experimental and Theoretical (MD/QM) Comparison. //J. Am. Chem. Soc., 2000.122(30): p. 7312−7316.
  112. Worthington S.E., M. Krauss, Effective fragment potentials and the enzyme active site. //Comput. Chem., 2000. 24(3−1): p. 275−285.
  113. Worthington S.E., A.E. Roitberg, M. Krauss, An MD/QM Study of the Chorismate Mutase-Catalyzed Claisen Rearrangement Reaction. // J. Phys. Chem. B, 2001. 105(29): p. 7087−7095.
  114. Ponder J.W. TINKER. Available from: http://dasher.wustl.edu/ffe/.
  115. Hu L., P. Soderhjelm, U. Ryde, On the Convergence of QM/MM Energies. // J. Chem. Theory Comput., 2011. 7(3): p. 761−777.
  116. Reuter N., A. Dejaegere, B. Maigret, M. Karplus, Frontier Bonds in QMJMM Methods: A Comparison of Different Approaches. // J. Phys. Chem. A, 2000. 104(8): p. 1720−1735.
  117. Schmidt H.H.H.W., F. Hofmann, J.P. Stasch, cGMP: generators, effectors and therapeutic implications. 2009: Springer Verlag.
  118. Ribeiro A.n.J.M., M.J. Ramos, P.A. Fernandes, Benchmarking of DFT Functionals for the Hydrolysis of Phosphodiester Bonds. // J. Chem. Theory Comput., 2010. 6(8): p. 2281−2292.
  119. Chen X., C.-G. Zhan, Fundamental Reaction Pathways and Free-Energy Barriers for Ester Hydrolysis of Intracellular Second-Messenger 3 ', 5 '-Cyclic Nucleotide. // J. Phys. Chem. A, 2004.108(17): p. 3789−3797.
  120. Grigorenko B.L., A.V. Rogov, A.V. Nemukhin, Mechanism of Triphosphate Hydrolysis in Aqueous Solution:? QM/MM Simulations in Water Clusters. // J. Phys. Chem. B, 2006.110(9): p. 4407−4412.
  121. Jorgensen W.L., J. Chandrasekhar, J.D. Madura, R.W. Impey, M.L. Klein, Comparison of simple potential functions for simulating liquid water. // J. Chem. Phys., 1983. 79(2): p. 926−935.
  122. Zhu X., P.E.M. Lopes, A.D. MacKerell Jr, Recent developments and applications of the CHARMM force fields. // Wiley Interdisciplinary Reviews: Computational Molecular Science.
  123. Phillips J.C., R. Braun, W. Wang, J. Gumbart, E. Tajkhorshid, E. Villa, C. Chipot, R.D. Skeel, L. Kale, K. Schulten, Scalable molecular dynamics with NAMD. // J. Comput. Chem., 2005. 26(16): p. 1781−1802.
  124. Yang Y., Q. Cui, Does Water Relay Play an Important Role in Phosphoryl Transfer Reactions? Insights from Theoretical Study of a Model Reaction in Water andtert-Butanol. //J. Phys. Chem. B, 2009.113(14): p. 4930−4939.
  125. Kamerlin S.C.L., M. Haranczyk, A. Warshel, Are Mixed Explicit/Implicit Solvation Models Reliable for Studying Phosphate Hydrolysis? A Comparative Study of Continuum, Explicit and Mixed Solvation Models. // ChemPhysChem, 2009.10(7): p. 1125−1134.
  126. Fuxreiter M., A. Warshel, Origin of the catalytic power of acetylcholinesterase: computer simulation studies. //J. Am. Chem. Soc., 1998.120(1): p. 183−194.
  127. Quinn D.M., Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transition states. //Chem. Rev., 1987. 87(5): p. 955−979.
  128. Rosenberry T.L., Strategies to resolve the catalytic mechanism of acetylcholinesterase. //Journal of molecular neuroscience, 2010. 40(1): p. 32−39.
  129. Taylor P., Z. Radic, The cholinesterases: from genes to proteins. //Annu. Rev. Pharmacool. Toxicol., 1994. 34(1): p. 281−320.
  130. Manojkumar T., C. Cui, K.S. Kim, Theoretical insights into the mechanism of acetylcholinesterase catalyzed acylation of acetylcholine. // J. Comput. Chem., 2005.26(6): p. 606−611.
  131. Sant’Anna C.M.R., A. dos Santos Viana, N.M. do Nascimento Junior, A semiempirical study of acetylcholine hydrolysis catalyzed by Drosophila melanogaster acetylcholinesterase. //Bioorg. Chem., 2006. 34(2): p. 77−89.
  132. Tachikawa H., M. Igarashi, J. Nishihira, T. Ishibashi, Ab initio model study on acetylcholinesterase catalysis: potential energy surfaces of the proton transfer reactions. //J. Photochem. Photobiol. B, 2005. 79(1): p. 11−23.
  133. Vagedes P., B. Rabenstein, J. Aqvist, J. Marelius, E.W. Knapp, The deacylation step of acetylcholinesterase: Computer simulation studies. // J. Am. Chem. Soc., 2000.122(49): p. 12 254−12 262.
  134. Wang Q., H. Jiang, J. Chen, K. Chen, R. Ji, On the possible reaction pathway for the acylation of AChE catalyzed hydrolysis of ACh: Semiempirical quantum chemical study. //Int. J. Quantum Chem., 1998. 70(3): p. 515−525.
  135. Wang Q.M., H.L. Jiang, K.X. Chen, R.Y. Ji, Y.J. Ye, Theoretical studies on the possible reaction pathway for the deacylation of the AChE catalyzed reaction. // Int. J. Quantum Chem., 1999. 74(3): p. 315−325.
  136. Wlodek S.T., J. Antosiewicz, J.M. Briggs, On the mechanism of acetylcholinesterase action: The electrostatically induced acceleration of the catalytic acylation step. //J. Am. Chem. Soc., 1997.119(35): p. 8159−8165.
  137. Nemukhin A.V., S.V. Lushchekina, A.V. Bochenkova, A.A. Golubeva, S.D. Varfolomeev, Characterization of a complete cycle of acetylcholinesterase catalysis by ab initio QM/MM modeling. // J. Mol. Model., 2008. 14(5): p. 409 416.
  138. Zhang Y., J. Kua, J.A. McCammon, Role of the catalytic triad and oxyanion hole in acetylcholinesterase catalysis: an ab initio QM/MM study. // J. Am. Chem. Soc., 2002.124(35): p. 10 572−10 577.
  139. Zhang Y., J. Kua, J.A. McCammon, Influence of structural fluctuation on enzyme reaction energy barriers in combined quantum mechanical/molecular mechanical studies. //J. Phys. Chem. B, 2003.107(18): p. 4459−4463.
  140. Zhou Y., S. Wang, Y. Zhang, Catalytic Reaction Mechanism of Acetylcholinesterase Determined by Born- Oppenheimer Ab Initio QM/MM Molecular Dynamics Simulations. //J. Phys. Chem. B, 2010. 114(26): p. 88 178 825.
  141. Lushchekina S., I. Kaliman, B. Grigorenko, A. Nemukhin, S. Varfolomeev, Quantum mechanical/molecular mechanical analysis of mechanisms of enzyme action. Human acetylcholinesterase. //Russ. Chem. Bull., 2011. 60(11): p. 21 962 204.
  142. Kwasnieski O., L. Verdier, M. Malacria, E. Derat, Fixation of the two Tabun isomers in acetylcholinesterase: a QM/MM study. // J. Phys. Chem. B, 2009. 113(29): p. 10 001−10 007.
  143. Tormos J.R., K.L. Wiley, Y. Wang, D. Fournier, P. Masson, F. Nachon, D.M. Quinn, Accumulation of Tetrahedral Intermediates in Cholinesterase Catalysis: A
  144. Secondary Isotope Effect Study. //J. Am. Chem. Soc., 2010. 132(50), p. 1 775 117 759
  145. Bourne Y., P. Taylor, P. Marchot, Acetylcholinesterase inhibition by fasciculin: crystal structure of the complex. //Cell, 1995. 83(3): p. 503−512.
  146. Tsien R.Y., The green fluorescent protein. //Annu. Rev. Biochem., 1998. 67(1): p. 509−544.
  147. Matz M.V., A.F. Fradkov, Y.A. Labas, A.P. Savitsky, A.G. Zaraisky, M.L. Markelov, S.A. Lukyanov, Fluorescent proteins from nonbioluminescent Anthozoa species. //Nat. Biotechnol., 1999.17(10): p. 969−973.
  148. Rao B.D.N., M. Kemple, F. Prendergast, Proton nuclear magnetic resonance and fluorescence spectroscopic studies of segmental mobility in aequorin and a green fluorescent protein from Aequorea forskalea. //Biophys. J., 1980. 32(1): p. 630 632.
  149. Ward W.W., S.H. Bokman, Reversible denaturation of Aequorea green-fluorescent protein: physical separation and characterization of the renatured protein. //Biochemistry, 1982. 21(19): p. 4535−4540.
  150. Labas Y.A., N. Gurskaya, Y.G. Yanushevich, A. Fradkov, K. Lukyanov, S. Lukyanov, M. Matz, Diversity and evolution of the green fluorescent protein family. //PNAS, 2002. 99(7): p. 4256.
  151. Zimmer M., Green fluorescent protein (GFP): applications, structure, and related photophysical behavior. //Chem Rev, 2002.102(3): p. 759−781.
  152. Bogdanov A.M., A.S. Mishin, I.V. Yampolsky, V.V. Belousov, D.M. Chudakov, F.V. Subach, V.V. Verkhusha, S. Lukyanov, K.A. Lukyanov, Green fluorescent proteins are light-induced electron donors. // Nat. Chem. Biol., 2009. 5: p. 459 461.
  153. Dikici E., S. Daunert, Engineering bioluminescent proteins: expanding their analytical potential. //Anal. Chem., 2009. 81(21): p. 8662−8668.
  154. Lippincott-Schwartz J., G.H. Patterson, Photoactivatable fluorescent proteins for diffraction-limited and super-resolution imaging. // Trends Cell Biol., 2009. 19: p.555−565.
  155. Lukyanov K.A., D.M. Chudakov, S. Lukyanov, V.V. Verkhusha, Photoactivatable fluorescent proteins. //Nat. Rev. Mol. Cell Biol., 2005. 6: p. 885.
  156. Patterson G.H., Highlights of the optical highlighter fluorescent proteins. // J. Microsc., 2011.243: p. 1−7.
  157. Subach F.V., V.N. Malashkevich, W.D. Zencheck, H. Xiao, G.S. Filonov, S.C. Almo, V.V. Verkhusha, Photoactivation mechanism of PAmCherry based on crystal structures of the protein in the dark and fluorescent states. // PNAS, 2009. 106: p. 21 097−21 102.
  158. Subach F.V., G.H. Patterson, M. Renz, J. Lippincott-Schwartz, V.V. Verkhusha, Bright monomeric photoactivatable red fluorescent protein for two-color superresolution sptPALM of live cells. //J. Am. Chem. Soc., 2010.132: p. 6481−6491.
  159. Langhojer F., F. Dimler, G. Jung, T. Brixner, Ultrafast photoconversion of the green fluorescent protein studied by accumulative femtosecond spectroscopy. // Biophys. J., 2009. 96: p. 2763−2770.
  160. Patterson G.H., J. Lippincott-Schwartz, A photoactivatable GFP for selective photolabeling ofproteins and cells. //Science, 2002. 297: p. 1873−1877.
  161. Henderson J.N., R. Gepshtein, J.R. Heenan, K. Kallio, D. Huppert, S.J. Remington, Structure and mechanism of the photoactivatable green fluorescent protein. //J. Am. Chem. Soc., 2009.131: p. 4176−4177.
  162. Bravaya K.B., A.V. Bochenkova, A.A. Granovsky, A.V. Nemukhin, Modeling photoabsorption of the asFP595 chromophore. //Russ. J. Phys. Chem. B, 2008. 2: p. 671−679.
  163. Bravaya K.B., B.L. Grigorenko, A.V. Nemukhin, A.I. Krylov, Quantum Chemistry Behind Bioimaging: Insights from Ab Initio Studies of Fluorescent Proteins and Their Chromophores. //Acc. Chem. Res., 2012. 45: p. 265−275.
  164. Das A.K., J.Y. Hasegawa, T. Miyahara, M. Ehara, H. Nakatsuji, Electronic excitations of the green fluorescent protein chromophore in its protonation states: SAC/SAC-CIstudy. //J. Comput. Chem., 2003. 24: p. 1421−1431.
  165. Filippi C., F. Buda, L. Guidoni, A. Sinicropi, Bathochromic shift in Green Fluorescent Protein: A puzzle for QM/MM approaches. // J. Chem. Theory Comput., 2012. 8: p. 112−124.
  166. Filippi C., M. Zaccheddu, F. Buda, Absorption Spectrum of the Green Fluorescent Protein Chromophore: A Difficult Case for ab Initio Methods? // J. Chem. Theory Comput., 2009. 5: p. 2074−2087.
  167. Hasegawa J.Y., K. Fujimoto, B. Swerts, T. Miyahara, H. Nakatsuji, Excited states of GFP chromophore and active site studied by the SAC-CI method: Effect of protein environment and mutations. // J. Comput. Chem., 2007. 28: p. 2443−2452.
  168. Laino T., R. Nifosi, V. Tozzini, Relationship between structure and optical properties in green fluorescent proteins: a quantum mechanical study of the chromophore environment. // Chem. Phys., 2004. 298: p. 17−28.
  169. Topol I., J. Collins, I. Polyakov, B. Grigorenko, A. Nemukhin, On photoabsorption of the neutral form of the green fluorescent protein chromophore. //Biophys. Chem., 2009.145: p. 1−6.
  170. Bravaya K.B., M.G. Khrenova, B.L. Grigorenko, A.V. Nemukhin, A.I. Krylov, Effect of Protein Environment on Electronically Excited and Ionized States of the Green Fluorescent Protein Chromophore. //J. Phys. Chem. B, 2011.115: p. 82 968 303.
  171. Sinicropi A., T. Andruniow, N. Ferre, R. Basosi, M. Olivucci, Properties of the emitting state of the green fluorescent protein resolved at the CASPT2//CASSCF/CHARMM level. //J. Am. Chem. Soc., 2005. 127: p. 1 153 411 543−11 535.
  172. Creemers T.M.H., AJ. Lock, V. Subramaniam, T.M. Jovin, S. Volker, Three photoconvertible forms of green fluorescent protein identified by spectral hole-burning. //Nat. Struct. Biol., 1999. 6: p. 557−560.
  173. Ormo M., A.B. Cubitt, K. Kallio, L.A. Gross, R.Y. Tsien, SJ. Remington, Crystal structure of the Aequorea victoria green fluorescent protein. // Science, 1996. 273: p. 1392−1395.
  174. Yang F., L.G. Moss, G.N. Phillips, The molecular structure of green fluorescent protein. //Nat. Biotechnol., 1996.14: p. 1246−1251. ,
  175. Ivanic J., Direct configuration interaction and multiconfigurational self-cons is tent-field method for multiple active spaces with variable occupations. I. Method. //J. Chem. Phys., 2003.119: p. 9364−9377.
  176. Granovsky A.A., Extended multi-configuration quasi-degenerate perturbation theory: The new approach to multi-state multi-reference perturbation theory. // J. Chem. Phys., 2011.134: p. 214 113−214 127.
  177. Granovsky A.A. Firefly. Available from: http://classic.chem.msu.su/gran/firefly/index.html.
  178. Grimme S., Improved second-order Moller-Plesset perturbation theory by separate scaling of parallel-and antiparallel-spin pair correlation energies. // J. Chem. Phys., 2003.118: p. 9095−9103.
  179. Rhee Y.M., M. Head-Gordon, Scaled second-order perturbation corrections to configuration interaction singles: Efficient and reliable excitation energy methods. //J. Phys. Chem. A, 2007. Ill: p. 5314−5326.
  180. Krylov A.I., Equation-of-motion coupled-cluster methods for open-shell and electronically excited species: The Hitchhiker’s guide to Fock space. // Annu. Rev. Phys. Chem., 2008. 59: p. 433−462.
  181. Nifosi R., Y. Luo, Predictions of novel two-photon absorption bands in fluorescent proteins. //J. Phys. Chem. B., 2007. Ill: p. 14 043−14 050.
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