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Solvation Models for Protein Folding

Solvation Models for Protein Folding. 서울대학교 화학부 석차옥. Water, everywhere!. 지구 표면의 70%. 인체의 70%. Water in Cell. But usual solvation model is. Solvation Model is Important for. Protein Folding Protein-Ligand Interaction Protein-Protein Interaction. Levels of Solvation Models.

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Solvation Models for Protein Folding

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  1. Solvation Models for Protein Folding 서울대학교 화학부 석차옥

  2. Water, everywhere! 지구 표면의 70% 인체의 70%

  3. Water in Cell But usual solvation model is

  4. Solvation Model is Important for Protein Folding Protein-Ligand Interaction Protein-Protein Interaction

  5. Levels of Solvation Models Surface area Continuum electrostatics Continuum (implicit water) Molecule (explicit water) - + - + - + - + =80 Fixed charge models Polarizable models

  6. Explicit Water Models • 용매(물) 분자와 용질 분자 모두 explicitly 고려 • Solvation effect는 저절로 얻어짐 • 계산이 비쌈 (90% 이상이 용매 계산에 소요. • 용매의 자유도에 대한 average 필요)

  7. Some Fixed Charge Water Models

  8. Limitations • Polarizability • Water in first solvation shell, active site or interior (Bulk와 다름) • Bond flexibility • Temperature dependence

  9. Implicit Models A Model for Solvation Free Energy

  10. Surface Area Based Models Simple & fast Eisenberg and McLachlan, Nature 1986

  11. Distance Dependent Dielectric 보통 : heuristic

  12. More sophisticated continuum dielectric models (PB, GB) charging + + Cavity - - - + Partial charge

  13. PB (Poisson-Boltzmann) • Solvent as a continuum dielectric: 이 가정 하에서는 정확 • 물 분자의 크기에 대한 고려는 없음. (first-shell solvation effect는 무시됨) • 미분 방정식을 수치해석적으로 품. (Delphi) Poisson part Boltzmann part

  14. Poisson part of PB (Reduces to Coulomb’s law for constant dielectric)

  15. Ion Contributions Debye-Huckel Theory: Ionic density in bulk soln In 1:1 salt solution:

  16. Boltzmann part of PB Nonlinear PB equation Linear PB equation: when ionic strength is not high

  17. Finite difference solution of PB Grid size: Focusing

  18. GRASP Red: negative Blue: positive

  19. Examples of Application Binding Dynamics

  20. GB (Generalized Born) • Solvent as a continuum dielectric: PB보다 계산이 빠르나 approximate • (PB 결과를 아주 잘 근사하게 parametrized) • Environment specific DDD로 생각할 수 있음

  21. Born Radius Exact for a sphere of radius R Effective Born radius 

  22. GB Solvation Free Energy

  23. How to get Born Radius? • Volume integral • Surface integral • Analytical approximations

  24. EEF1 Vj 용질이 용매의 부피를 대체함으로서 발생하는 solvation free energy의 변화 고려. assumed to be Gaussian

  25. Successful example of use of EEF1 The best in the 10 year history of CASP ab initio prediction

  26. Break down of implicit solvation models

  27. Summary: Solvation Models More Physical, More expensive Surface area Distance dependent dielectric EEF1 Generalized Born Poisson-Boltzmann Implicit Explicit 단백질 구조예측 Fixed-charge explicit solvent Dynamics Simulation

  28. Thank You, andEnjoy Water!!!

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