QM/MM Modelling

Lecture 3Some Application Examples

Workshop Example cases for this afternoon

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 Application

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

Some sample clusters on the ZnO surface

Methanol 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

Workshop examples

• Simple QM and MM calculations using ChemShell

SN2 TS (CH3Cl + Cl-) with explicit solvent

• task -> optimise, qm/mm

• load from mini_ts.pdb

• QM code to mndo

• QM Charge to -1

• DLPOLY FF - choose “use charmm”

• optimiser -> hdlcopt

• check find ts

• residue_treatment to “PDB Residues/Select”