直接计算蛋白质能量的分子力学方法
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Only nearest-neighbour fragment interaction is included In this standard MFCC approach
GMFCC
The interaction energy between non-neighboring residues in close contact
Weak interaction is very important in protein interaction and HF/DFT calculations are Incapable of giving dispersion energies,
Relative energy of the ace-α-(ala)15-nme, FS(HF/6-31G*): full system results calculation at HF/6-31G*; GMFCC-MM (HF/6-31G*): energy for relative energy calculated using Eq.(3) At HF/6-31G*; AMBER: relative energy using AMBER force field parm99; GMFCC-MM(MP2/6-31G*): energy for relative energy calculated using Eq. (3) at MP2/6-31G*
1. Background
1. Typical protein-ligand system contains thousands of atoms. 2. Standard quantum chemistry calculation is not practical 3. Current linear scaling methods are limited to semiempirical calculations 4. QM/MM methods are gaining popularity 5. Classical force field (FF) is currently the dominant approach 6. Development of Molecular fractionation with conjugate
➢
No date communication: parallel computation
5) Computationally efficient and linear scaling
➢
Machine: Pentium4, 1Gbyte random access memory (RAM)
➢
GMFCC/MM: SP 1VTP (26 residues), MP2/6-31G*, 23h and 30 min
caps (MFCC)
2. GMFCC/MM idea
• GMFCC: The short range non-neighboring fragment interactions
• MM: The long range interaction between distant non-
neighboring fragments
4. Attractive features:
1) No need to construct the density matrix or Hamiltonian of the entire Molecular system.
2) No need to diagonalize the full Hamiltonian matrix which will be the bottleneck in linear-scaling calculation of large molecular system
GMFCC/MM
EQM (nn): the interaction energy between non-neighboring fragments that are in close contact and to be calculated by quantum mechanics
EMM (nn): the rest of the interaction energy between non-neighboring (noconcaped) fragments excluding the quantum interaction energy EQM(nn)
borrowed from QM/MM long-range electrostatic and van der Waals interaction All the parameters used in this study are from pa源自文库m99 in AMBER8
3.Tested polypeptide systems10
the MFCC scheme to cut protein into amino-acid fragments
Ek: the total energy of the kth (capped fragment) Ekcc: the energy of the kth concap E MM (nn): the MM energy between non-neighboring fragments EMFCC: the MFCC combination of energies
The Generalized Molecular Fractionation With Conjugate Caps/Molecular Mechanics (GMFCC/MM) Method for Direct Calculation of Protein Energy
Outline
• 1. Background • 2. GMFCC/MM • 3. Tested polypeptide systems • 4. Attractive features
3) Allowing one to perform quantum chemistry calculation at higher levels of electron correlation beyond HF and DFT.
4) GMFCC/MM approach applies to the entire protein system, not just the small reaction center that is treated by quantum mechanics in a standard QM/MM methods.
GMFCC
The interaction energy between non-neighboring residues in close contact
Weak interaction is very important in protein interaction and HF/DFT calculations are Incapable of giving dispersion energies,
Relative energy of the ace-α-(ala)15-nme, FS(HF/6-31G*): full system results calculation at HF/6-31G*; GMFCC-MM (HF/6-31G*): energy for relative energy calculated using Eq.(3) At HF/6-31G*; AMBER: relative energy using AMBER force field parm99; GMFCC-MM(MP2/6-31G*): energy for relative energy calculated using Eq. (3) at MP2/6-31G*
1. Background
1. Typical protein-ligand system contains thousands of atoms. 2. Standard quantum chemistry calculation is not practical 3. Current linear scaling methods are limited to semiempirical calculations 4. QM/MM methods are gaining popularity 5. Classical force field (FF) is currently the dominant approach 6. Development of Molecular fractionation with conjugate
➢
No date communication: parallel computation
5) Computationally efficient and linear scaling
➢
Machine: Pentium4, 1Gbyte random access memory (RAM)
➢
GMFCC/MM: SP 1VTP (26 residues), MP2/6-31G*, 23h and 30 min
caps (MFCC)
2. GMFCC/MM idea
• GMFCC: The short range non-neighboring fragment interactions
• MM: The long range interaction between distant non-
neighboring fragments
4. Attractive features:
1) No need to construct the density matrix or Hamiltonian of the entire Molecular system.
2) No need to diagonalize the full Hamiltonian matrix which will be the bottleneck in linear-scaling calculation of large molecular system
GMFCC/MM
EQM (nn): the interaction energy between non-neighboring fragments that are in close contact and to be calculated by quantum mechanics
EMM (nn): the rest of the interaction energy between non-neighboring (noconcaped) fragments excluding the quantum interaction energy EQM(nn)
borrowed from QM/MM long-range electrostatic and van der Waals interaction All the parameters used in this study are from pa源自文库m99 in AMBER8
3.Tested polypeptide systems10
the MFCC scheme to cut protein into amino-acid fragments
Ek: the total energy of the kth (capped fragment) Ekcc: the energy of the kth concap E MM (nn): the MM energy between non-neighboring fragments EMFCC: the MFCC combination of energies
The Generalized Molecular Fractionation With Conjugate Caps/Molecular Mechanics (GMFCC/MM) Method for Direct Calculation of Protein Energy
Outline
• 1. Background • 2. GMFCC/MM • 3. Tested polypeptide systems • 4. Attractive features
3) Allowing one to perform quantum chemistry calculation at higher levels of electron correlation beyond HF and DFT.
4) GMFCC/MM approach applies to the entire protein system, not just the small reaction center that is treated by quantum mechanics in a standard QM/MM methods.