1. Lecture 3 QM/MM Applications

2. 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

3. 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 N 2 O abatement (with Daresbury)

4. 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

5. Solvation studies using QM/MM

6. 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

7. 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 CH 4 + D +  CH 3 D + H +

8. QUASI - Applications Focus ¤Norsk Hydro / Daresbury Zeolites systems with adsorbed Cu species, decomposition of N 2 O and NO x 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

9. Embedded cluster and QM/MM Applications Proton transfer (ZOH + + NH 3 -> ZO - + NH 4 + ) ¤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)

10. 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 Al O HD C HH

11. 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 H q=0 q=q Si + 0.5*q O

12. 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)

13. 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 Al O H2CH2C CH 2 CH 3 Si O Al O CH 2 H2CH2C CH 3 Si O Al O H2CH2C CH 2. CH 3

14. 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.

15. Methyl Shift of Propenium: Conclusions Mechanical factors ¤transition state fits better into the zeolite framework structure than the propoxide minima Electrostatic embedding ¤all QM clusters are stabilised by electrostatic interactions,but smaller effects on relative energies ¤one barrier increases, one decreases MM polarisation ¤transition state has a larger dipole moment than minima (11 vs 6 D) ¤MM polarisation stabilises the charge separation, lowering both barriers

16. QUASI Zeolite catalysis applications Demonstration phase NO, NO 2 (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 N 2 O, N 2 and O 2 Target Applications N 2 O (off-gas from HNO 3 production) ¤Binding of N 2 O with the active site ¤Binding energies and vibrational frequencies ¤Thermodynamics of N 2 O decomposition pathways ¤Influence of other components of the off-gas (O 2, NO x,H 2 O), inhibitor action, binding energies etc. NO x decomposition on zeolite supported copper catalysts Lead Partner: Norsk Hydro

17. 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)

18. 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

19. 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 of DHAP to GAP Demonstration case within QUASI (Partners UZH, and BASF) QM/MM Applications

20. Enzyme QM/MM Applications - TIM

21. 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. Zn 2+, O 2- ) 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

22. 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

23. 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, 13 C chemical shifts ¤Transition states for proton and hydride transfer steps ¤Understanding promoter action Methanol synthesis from synthesis gas (CO, CO 2 and H 2 ) using the ternary catalyst system Cu/ZnO/Al 2 O 3 e.g. CO + 2H 2 -> CH 3 (OH) Lead Partner: ICI

24. 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

25. Methonol Synthesis Reaction Initial adsorption of CO 2 and H 2. Upon adding an electron the CO 2 bends and the extra electron populates an antibonding level. The interaction with the surface stabilises the radical CO 2 - species. The adsorbed CO 2 - is hydrogenated by surface hydrogen to formate. Further hydrogenation can proceed either through the formation of H 2 CO 2 - 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

26. Adsorption of copper clusters

27. 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