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Quantum Biochemistry
Jan H. Jensen University of Copenhagen
Download the slides at:
h:p://<nyurl.com/padsgs8
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Quantum Biochemistry
Enzyme catalysis Protein-‐ligand binding
QM/MM
MM-‐Parameters
Boundary
Linear-‐Scaling
Slow geometry op<miza<on
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Blurring the boundary between linear scaling QM, QM/MM and polarizable force fields
The Effec(ve Fragment Molecular Orbital Method
Jan H. Jensen, Anders Christensen and Casper Steinmann (SDU) University of Copenhagen
Dmitri Fedorov AIST, Japan
JPC A 2010, 114, 8705 PLoS ONE 2012, 7:e41117 PLoS ONE 2012, 7:e44480 PLoS ONE 2013, 8: e60602
arxiv:1305.0676
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The EffecDve Fragment Molecular Orbital (EFMO) method (Using ideas from the Effec<ve Fragment Poten<al (EFP) method)
Monomer SCF in the gas phase
Extract mul<poles and dipole polarizability
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The EffecDve Fragment Molecular Orbital (EFMO) method (Using ideas from the Effec<ve Fragment Poten<al (EFP) method)
Many-‐body polarizaDon
Computed classically using induced dipoles for en<re system
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The EffecDve Fragment Molecular Orbital (EFMO) method (Using ideas from the Effec<ve Fragment Poten<al (EFP) method)
Coulomb and Non-‐Coulomb effects
dimer SCF in the gas phase
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The EffecDve Fragment Molecular Orbital (EFMO) method (Using ideas from the Effec<ve Fragment Poten<al (EFP) method)
Coulomb effects
Computed using sta<c mul<poles
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Covalent FragmentaDon (Electrosta<c screening crucial)
8 PLoS ONE 2012, 7:e44480
QM/”MM”
Ac<ve
Frozen
EEFMO = EA + EA /F + EF
EEFMO = EA0 + EAJ
0 − EA0 − EJ
0 − EIJPOL( )
J∈F
RI ,J ≤Rcut
∑ + EAJES
J∈F
RI ,J >Rcut
∑ + EtotPOL
PLoS ONE 2013, 8: e60602 9
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Proof-‐of-‐concept PLoS ONE 2013, 8: e60602
ONIOM: MP2/cc-‐pVDZ:EFMO-‐RHF/6-‐31G(d)
16 Å
ΔH ≠ = 18 vs 13 (exp)
4 days/path 80 CPUs
Where do we go from here?
EFMO/PCM
Open Shell
Frequencies
Large-‐scale QM op<miza<on s<ll too slow:
MP2:RHF(-‐D) op<miza<on*
DFT:HF-‐3c#
DFT:PM6-‐DH+
*Christensen, arxiv:1305.0676 #Grimme, J. Comp. Chem. early view
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Thank you
QuesDons?
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