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Transcript of Lecture 3 QM/MM Applications. Quantum Simulation in Industry Overview ¤Objectives Extend QM/MM...
Lecture 3
QM/MM Applications
Quantum Simulation in Industry
Overview¤ Objectives
• Extend QM/MM Codes and port to HPC architectures• Incorporate QM/MM molecular dynamics for chemical reactions• Demonstrate the value of HPC simulations in industrial chemistry
¤ Consortium• Daresbury (Coordinator)• Academic (Zurich/Muelheim, Royal Institution)• Industrial (Norsk Hydro, BASF, ICI)
¤ Resources• Funded by the European Union (EU contribution of 1.2 MECU)• 1998-2001
http://www.cse.clrc.ac.uk/Activity/QUASI
QUASI - Partners
¤ Drs Paul Sherwood, Martyn Guest (Daresbury Laboratory) • Coordinator• Ab-initio and HPC implementations• ChemShell software
¤ Prof Walter Thiel (MPI Muelheim) • Semi-emprical (MNDO94), QM/MM coupling
¤ Prof Richard Catlow (Royal Insitution) • Classical simulation, shell model, force field derivation
¤ Dr Steve Rogers (ICI)• Methanol synthesis by metal oxide catalysts (with Royal Institution)
¤ Dr Ansgar Schaeffer (BASF)• Enzyme inhibitor simulation (with Zurich)
¤ Dr Klaus Schoeffel (Norsk Hydro) • Zeolite catalysis for N2O abatement (with Daresbury)
QUASI - Workplan
• Design¤ QM and MM validation
¤ QM/MM coupling approaches (Daresbury,Zurich)
• Enhancements to QM/MM Methodology¤ Geometry Optimisation for QM/MM Systems (Zurich/Daresbury)
¤ Classical Shell Model QM/MM (Royal Institution/Daresbury)
¤ Molecular Dynamics (DL/Royal Institution)
¤ GUI Development (BASF/Daresbury)
¤ Forcefield Development (Royal Institition)
• Joint Academic/Industrial Applications¤ Demonstration and Commercial Calculations
¤ Workshop 25-27 September 2000, Muelheim, Germany
Solvation studies using QM/MM
Hybrid modelling for zeolites
• CVFF (Hill/Sauer forcefield)• Construct finite cluster
(termination using charge corrections fitted to Ewald sum)
• QM Model comprises T5 cluster + Cu, NO etc
• Electrostatic embedding
The D/H Exchange Reaction
¤ Collaboration with Shell KSLA
¤ A symmetrical model for protonation reaction by zeolite Bronsted acid site
¤ Extensively studied with bare cluster models
¤ Study effects of zeolite environment by considering a range of possible acid sites
• Embedding geometry• Electrostatics• Correlation with adsorbtion
energies and acidities
¤ Geometrical effects on the transition state are found to be dominant
CH4 + D+ CH3D + H+
QUASI - Applications Focus
¤ Norsk Hydro / Daresbury• Zeolites systems with adsorbed Cu species, decomposition of N2O and
NOx
• Based on CFF forcefield, GAMESS-UK+DL_POLY
¤ BASF / Muelheim• Enzyme inhibitor binding (thrombin and anticoagulant drug candidates)• Enzyme reactivity modelling (Triose Phosphate Isomerase)• Using MNDO/TURBOMOLE with CHARMM forcefield (DL_POLY)
¤ ICI/ Royal Institution• Modelling surface catalysis, methanol synthesis reaction• Using GULP shell model potentials and GAMESS-UK DFT
Embedded cluster and QM/MM Applications
• Proton transfer (ZOH+ + NH3 -> ZO- + NH4+)
¤ S.P. Greatbanks, I.H.Hillier and P. Sherwood, J. Comp. Chem., 18, 562, 1997.
• Methyl shift reaction of propenium ion¤ P. Sherwood, A.H. de Vries, S.J. Collins, S.P.Greatbanks, N.A. Burton,
M.A. Vincent and I.H. Hillier, Faraday Discuss., 106, 1997
• Alkene chemisorption ¤ P.E. Sinclair, A.H. de Vries, P. Sherwood, C.R.A. Catlow and R.A. Van
Santen, J. Chem. Soc., Faraday Trans.,94, 3401, 1998
• D/H exchange reaction for methane¤ A.H. de Vries, P. Sherwood, S.J.Collins, A.M. Rigby, M. Rigutto and G.J.
Kramer, J. Phys. Chem. B, 103, 6133 (1999)
Methane D/H Exchange Reaction
• A. H. de Vries, in collaboration with Shell IOP, Amsterdam
• A degenerate model reaction for acid-catalysed cracking processes
• Rates experimentally accessible for a range of systems
• Studied by QM/MM for a range of zeolite sites
H
Si
O
SiAl
O
H D
C
H H
D/H Exchange - Methodology
• QM/MM Scheme¤ T5 QM region, electrostatic embedding, 3-21G
geometries and 6-31G* energies
¤ 1500 atom finite MM cluster, Madelung correction
¤ Si-H termination
¤ Delete bond dipole contributions, apply charge shift and dipole correction
¤ CFF valence forcefield (Hill and Sauer)
¤ Electrostatics from charges fitted to Periodic HF potentials
• Geometry Optimisation¤ relaxation of 5 bonds from QM region
¤ P-RFO in mixed Z-matrix/cartesian coordinates
Si
O
Si
Hq=0
q=qSi + 0.5*qO
D/H Exchange Reaction - Results
• Relaxation and TS searching for embedded models now practical• Can differentiate of protonation energies for the 4 distinct oxygen sites
(FAU)¤ correctly predict protonation at O3 (at 6-31G*), with O1 site slightly
(1kJ/mol) higher
• Results emphasise importance of mechanical constraints¤ Highest activation energies can be identified with sites with non-planar Si-
O-Al-O-Si fragments¤ For remaining structures, a strong correlation seen between activation
energy of D/H exchange with the chemisorption energy of ammonium (analogous bidentate structures)
• Absolute values of D/H exchange activation energies too high (single point MP2 correction based on HF structures)¤ 160 (computed) vs 109 +/- 15 kJ/mol (MFI)¤ 175 (computed) vs 129 +/- 20 kJ/mol (FAU)
Methyl shift of the propenium ion
¤ QM/MM model similar to previous case
¤ Optimise end-points (propoxides) and transition state • mechanical embedding
– no charges on QM region, only includes geometric/steric effects• electrostatic embedding
– introduce QM charge interaction with MM lattice
Si
O
SiAl
O
H2CCH2
CH3
Si
O
Si Al
O
CH2
H2C
CH3
Si
O
SiAl
O
H2C CH2.
CH3
Analysis of Energy Barriers
¤ Mechanical embedding case is easy to decompose into QM and MM terms• Z-(C,H) nb is the zeolite…hydrocarbon non-bonded energy
¤ QM-MM Electrostatic interaction is estimated by calculating interaction of a classical representation of the QM region (Dipole Preserving Charges, DPC) with the MM point charges
¤ Role of MM polarisation is estimated using single-point calculation of interaction of DPC representation of QM region with polarisabilities at Si and O sites.
model energy Propoxide I TS Propoxide 2 Barrier I Barrier II
Gas phase Total 0 316 0 316 316
Mechanical Total 0 247 55 247 192
QM 0 261 38 261 223
MM 0 -6 9 -6 -15
Z-(C,H) n.b. -12 -20 -4 -8 -16
Electrostatic Total 0 253 68 253 185
QM-MM Elec -93 -103 -100 10 -3
Polarised QM-MM Pol -30 -45 -33 -15 -12
QUASI Zeolite catalysis applications
Demonstration phaseNO, NO2 (Automotive exhaust gas)
¤ Energetics and structure of Cu species coordinated to the zeolite framework.
¤ Absorbed Cu-NO species, structure and vibrational spectra
¤ Decomposition chemistry of NO to N2O, N2 and O2
Target ApplicationsN2O (off-gas from HNO3 production)
¤ Binding of N2O with the active site
¤ Binding energies and vibrational frequencies
¤ Thermodynamics of N2O decomposition pathways
¤ Influence of other components of the off-gas (O2, NOx ,H2O), inhibitor action, binding energies etc.
NOx decomposition on zeolite supported copper catalysts
Lead Partner: Norsk Hydro
Enzyme catalysis applications
Demonstration phase
¤ Variation of inhibitor binding enthalpies and free energies with QM region and electrostatic interactions
¤ Determination of activation energies, variation with QM scheme and QM/MM coupling.
¤ Comparison of substrate structure with X-ray results
Target Applications
¤ Influence of active site features on inhibitor binding energies and activation energies.
¤ Systematic study of free energies of binding for novel inhibitors, inhibitor design
¤ Understanding the mechanism of TIM action.
Lead Partner: BASF
• Enzyme/inhibitor binding energetics for thrombin• Mechanistic studies of enzyme catalysis - triosephosphate
isomerase (TIM)
Hybrid models for enzymes
• Electrostatic embedding (L1 for semi-empirical, L2 and charge shift schemes)
• QM: MNDO and TURBOMOLE • MM: DL_POLY (CHARMM
forcefield)• QM/MM cutoffs based on
neutral groups
• QM region (>33 atoms) – include residues with possible proton donor/acceptor roles – GAMESS-UK, MNDO, TURBOMOLE
• MM region (4,200 atoms + solvent)– CHARMM force-field, implemented in CHARMM, DL_POLY
Triosephosphate isomerase (TIM)
• Central reaction in glycolysis, catalytic interconversion ofDHAP to GAP
• Demonstration case within QUASI (Partners UZH, and BASF)
QM/MM Applications
Enzyme QM/MM Applications - TIM
QM
Solid-state Embedding Scheme
• Classical cluster termination¤ Base model on finite MM cluster¤ QM region sees fitted correction
charges at outer boundary
• QM region termination¤ Ionic pseudopotentials (e.g. Zn2+,
O2-) associated with atoms in the boundary region
• Forcefield¤ Shell model polarisation¤ Classical estimate of long-range
dielectric effects (Mott/Littleton)
• Energy Expression¤ Uncorrected
• Advantages¤ suitable for ionic materials
• Disadvantages¤ require specialised pseudopotentials
• Applications¤ metal oxide surfaces
MM
Implementation of solid-state embedding
¤ Under development by Royal Institution and Daresbury
¤ Based on shell model code GULP, from Julian Gale (Imperial College)
¤ Both shell and core positions appear as point charges in QM code (GAMESS-UK)
¤ Self-consistent coupling of shell relaxation
• Import electrostatic forces on shells from GAMESS-UK
• relax shell positions
GULP shell relaxation
GAMESS-UK SCF & shell forces
GAMESS-UK atomic forces
GULP forces
QUASI - Surface catalysis applications
Demonstration phase
¤ Geometry and electronic structure of bulk and surface QM clusters as a function of cluster size.
¤ Adsorption of Cu(I) on the ZnO surface
¤ Absorption energies, IR spectra and PES for CO on Cu and Zn sites
Target Applications
¤ Stability of Cu clusters of different sizes and ox. states
¤ Structure and energetics of absorption for formate, methoxy and carbonate on the surface, 13C chemical shifts
¤ Transition states for proton and hydride transfer steps
¤ Understanding promoter action
Methanol synthesis from synthesis gas (CO, CO2 and H2) using the ternary catalyst system Cu/ZnO/Al2O3
e.g. CO + 2H2 -> CH3(OH)
Lead Partner: ICI
Solid-state embedding for oxide surfaces
• Finite cluster model, outer sleeve of fitted charges charges from 2D Ewald summation
• QM: GAMESS-UK• MM: GULP• Solid-state embedding
scheme¤ Based on ZnO shell
model potential¤ Boundary atoms
carrying both shell model forcefield and pseudopotentials
Methonol Synthesis Reaction
• Initial adsorption of CO2 and H2.
• Upon adding an electron the CO2 bends and the extra electron populates an antibonding level. The interaction with the surface stabilises the radical CO2
- species.
• The adsorbed CO2- is hydrogenated
by surface hydrogen to formate.• Further hydrogenation can proceed
either through the formation of H2CO2-
or HCOOH- (formic acid)
• Further hydrogenation and interactions of the resulting species with the surface and possible surface defects lead to a large variety of possible intermediates.
• Methanol is removed from the surface and the active site is recycled by desorption of carbon dioxide and water
Adsorption of copper clusters
Acknowledgements
• QUASI software developments¤ Geometry optimisation, CHARMM interfacing, G98 interface
• Walter Thiel, Frank Terstegen, Salomon Billeter, Alex Turner
¤ TURBOMOLE interface• Ansgar Schäfer, Christian Lennartz
¤ Solid-state embedding• Alexei Sokol, Sam French, Richard Catlow
• Other Collaborators¤ CHARMM/GAMESS-UK
• Bernie Brooks, Eric Billings
¤ ChemShell developments, models for zeolites• Alex de Vries, Simon Collins, Ian Hillier, Steve Greatbanks• CEC, Shell SIOP Amsterdam