1. Paul Sherwood CLRC Daresbury Laboratory p.sherwood@dl.ac.uk
ChemShell
Paul Sherwood
CLRC Daresbury Laboratory

2. Overview ChemShell overview Introduction to Tcl Script basics
Modules overview
creating Input data objects
dl_poly
gamess
QM/MM Methods
hybrid
QM/MM models available
Input examples
ChemShell GUI

3. ChemShell Extended Tcl Interpreter Scripting capability
Interfaces to a range of QM and MM codes including
GAMESS-UK
DL_POLY
MNDO97
TURBOMOLE
CHARMM
GULP
Gaussian94
Implementation of QM/MM coupling schemes
link atom placement, forces etc
boundary charge corrections

4. ChemShell Architecture - Languages
An extended Tcl interpeter, written in..
Tcl
Control scripts
Interfaces to 3rd party executables
GUI construction (Tk and itcl)
Extensions C
Tcl command implementations
Object management (fragment, matrix, field, graph)
Tcl and C APIs
I/O
Open GL graphics
Fortran77
QM and MM codes: GAMESS-UK, GULP, MNDO97, DL_POLY

5. ChemShell Architecture
Core
ChemShell Tcl interpreter, with code to support chemistry data:
Optimiser and dynamics drivers
QM/MM Coupling schemes
Utilities
Graphics
GAMESS-UK (ab-initio, DFT)
MNDO (semi-empirical)
DL_POLY (MM)
GULP (Shell model, defects)
Features
Single executable possible
Parallel implementations
External Modules
CHARMM
TURBOMOLE
Gaussian94
MOPAC
AMBER
CADPAC
Features
Interfaces written in Tcl
No changes to 3rd party codes

6. ChemShell basics ChemShell control files are Tcl Scripts
Usually we use a .chm suffix
ChemShell commands have some additional structure, usually they take the following form
command arg1=value1 arg2=value2
Arguments can serve many functions
mm_defs=dl_poly.ff Identify a data file to use
coords=c Use object c as the source of the structure
use_pairlist=yes Provide a Boolean flag (yes/no, 1/0,, on/off)
list_option=full Provide a keyword setting
theory=gamess Indicate which compute module to use
Sometimes
command arg1=value1 arg2=value2 data

7. Very Simple Tcl (i) Variable Assignment (all variables are strings)
set a 1
Variable use
[ set a ] $a
Command result substitution
[ <Tcl command> ]
Numerical expressions
set a [ expr 2 * $b ]
Ouput to stdout
puts stdout “this is an output string”

8. Very Simple Tcl (ii)
Lists - often passed to ChemShell commands as arguments
set a { }
set a “1 2 3”
set a [ list ]
$ is evaluated within [ list .. ] and “ “ but not { }
[ list … ] construct is best for building nested lists using variables
Arrays - not used in ChemShell arguments, useful for user scripts
Associative - can be indexed using any string
set a(1) 1
set a(fred) x
parray a

9. Very Simple Tcl (iii) Continuation lines: can escape the newline
tclsh % set a “this \
is \
a single variable”
this is a single variable
tclsh %
{ } will incorporate newlines into the list
tclsh % set a {this is
a single variable}
this
a single variable
tclsh %

10. Very Simple Tcl (iv) Procedures Files
Sometimes needed to pass to ChemShell commands to provide an action
proc my_procedure { my_arg1 my_arg2 args } {
puts stdout “my_procedure”
return “the result” }
Files
set fp [ open my.dat w ]
puts $fp “set x $x”
close $fp
…..
source my.dat

11. ChemShell Object types
fragment - molecular structure
creation: c_create, load_pdb …. Universal!!
zmatrix
z_create, newopt, z_surface
matrix
creation: create_matrix, energy and gradient evaluators, dynamics
field
creation: cluster_potential etc, graphical display, charge fits
GUI only
3dgraph

12. ChemShell Object Representations
Between calculations, and sometimes between commands in a script, objects are stored as files. Usually there is no suffix, objects are distinguished internally by the block structure.
% cat c
block = fragment records = 0
block = title records = 1
phosphine
block = coordinates records = 34
p e e e-16
c e e e+00
c e e e-01
c e e e+00
c e e e+00
……....
Multi block objects are initiated by an empty block (e.g. fragment)
Unrecognised blocks are silently ignored

13. Object Caching
During a run objects can be cached in memory, the command to request this is the name of the object (similar to a declaration in a compiled language) #
fragment c
c_create coords=c {
h 0 0 0
h 0 0 1 }
list_molecule coords=c
delete_object c
# No file is created here
Confusion of objects with files can lead to confusion!!

14. Object Input and Output
If you access an object from a disk, ChemShell will always update the disk copy when it has finished (there is no easy way of telling if a command or procedure has changed it).
Usually this is harmless (e.g. output formats are precise enough), but unrecognised data in the input will not be present in the output, take a copy if you need to keep it.
E.g. if a GAMESS-UK punchfile contains a fragment object and a single data field (e.g. the potential) you can use it as both a fragment object and a field object
% rungamess test
% cp test.pun my_structure
% cp test.pun my_field
% chemsh
…….

15. Energy Gradient Evaluators
Many modules are designed to work with a variety of methods to compute the energy and gradient. The procedure relies on
the interfaces to the codes being consistent, each comprises a set of callable functions e.g.
initialisation
energy, gradient
kill
update
the particular set of functions being requested by a command option, usually theory=
Example evaluators (depends on locally available codes)
gamess, turbomole
dl_poly, charmm
mopac, mndo
hybrid
You can write your own in Tcl

16. Module options, using the :
The : syntax is used to pass control options to sub-module.
e.g. when running the optimiser, to set the options for the module computing the energy and gradient. {} can be used if there is more than one argument to pass on. Nested structures are possible using Tcl lists
newopt function=zopt : { theory=gamess : { basis=sto3g } zmatrix=z }
gamess arguments
Command
zopt arguments
newopt arguments

17. Loading Objects - Z-matrices
z_create zmatrix=z {
zmatrix angstrom c
x 1 1.0
n 1 cn 2 ang
f 1 cf 2 ang 3 phi
variables cn cf
phi
constants
ang
end }
z_list zmatrix=z
set p [ z_prepare_input zmatrix=z ]
puts stdout $p
z_create provides input processor for the z-matrix object
z_list can be used to display the object in a readable form
z_prepare_input provides the reverse transformation if you need something to edit
z_to_c provides the cartesian representation

18. Additional Z-matrix features (i)
Can include some atoms specified using cartesian coordinates
Can use symbols for atom-path values (i1,i2,i3)
Can append % to symbols to make them unique (e.g. o%1)
Can create/destroy and set variables using Tcl commands
z_create zmatrix=z1 {
zmatrix
o%1
o%2 o%1 3.
h%1 o% o%
h%2 o% o% h%1 29.0
end }
z_var zmatrix=z1 result=z2 control= "release all"
z_substitute zmatrix=z2 values= {r2=3.0 r3=2.0}
z_list zmatrix=z2

19. Additional Z-matrix features (ii)
Combine cartesian and internal definitions
z_create zmatrix=z1 {
coordinates
...
zmatrix
....
end }
c_to_z will create a fully cartesian z-matrix

20. Loading Data Object - Coordinates
c_create coords=h2o.c {
title
water dimer
coordinates au o h h o h h }
No symbols allowed
Can also use read_xyz, read_pdb, read_xtl

21. Periodic Systems (i)
Crystallographic cell constants can be provided, along with fractional coordinates #
c_create coords=mgo.c {
space_group 1
cell_constants angstrom
coordinates Mg O Mg O Mg O Mg O }
list_molecule coords=c
set p [ c_prepare_input coords=c ]

22. Periodic Systems (ii)
Alternatively, input the cell explicitly, in c_create or attach to the structure later #
c_create coords=d {
title
primitive unit cell of diamond
coordinates au c c
cell au }
extend_fragment coords=d cell_indices= { } result=d2
set_cell coords=d cell= { }

23. Core modules: DL_POLY Features
Energy and gradient routines from DL_POLY (Bill Smith UK, CCP5)
General purpose MM energy expression, including approximations to
CFF91 (e.g. zeolites)
CHARMM
AMBER
MM2
Topology generator
automatic atom typing
parameter assignment based on connectivity
topology from CHARMM PSF input
FIELD, CONFIG, CONTROL are generated automatically
FIELD is built up using terms defined in the file specified by mm_defs= argument
Periodic boundary conditions are limited to parallelopiped shaped cells
Can have multiple topologies active at one time

24. DL_POLY forcefield terms
Terms are input using atom symbols (or * wild card)
Individual keyword terms:
bond mm2bond quarbond angle mm2angle quarangle ptor mm2tor htor cfftor aa-couple aat-couple vdw powers m_n_vdw 6_vdw mm2_vdw
Input units are kcal/mol, angstrom etc in line with most forcefield publications
For full description see the manual

25. Automatic atom type assigment
Forcefield definition can incorporate connectivity-based atom type definitions which will be used to assign types
Atom types are hierarchical, most specific applicable type will be used (algorithm is iterative)
e.g. to use different parameters for ipso-C of PPh3 define a new type by a connection to phosphorous
query ci "ipso c"
supergroup c
target c
atom p
connect 1 2
endquery
charge c -0.15
charge h 0.15

26. DL_POLY Example # dummy forcefield read_input dl_poly.ff {
bond c c
bond c h
angle c c c
angle c c h
vdw h h
vdw c c
vdw h c
htor c c c c i-j-k-l
charge c -0.15
charge h 0.15 }
energy theory=dl_poly : mm_defs = dl_poly.ff coords=c energy=e

27. Using DL_POLY with CHARMM Parameters
Replicates CHARMM energy expression (without UREY)
Uses standard CHARMM datafiles
Requires CHARMM program + script to run as far as energy evaluation for initial setup
Atom charges and atom types are obtained by communication with a running CHARMM process (usually only run once)
# run charmm using script provided
charmm.preinit charmm_script=all.charmm coords=charmm.c
# Store type names from the topology file
load_charmm_types2 top_all22_prot.inp charmm_types
# These requires CTCL (i.e. charmm running)
set types [ get_charmm_types ]
set charges [ get_charmm_charges ]
set groups [ get_charmm_groups ] #
charmm.shutdown

28. Using DL_POLY with CHARMM Parameters
Then provide dl_poly interface with
.psf (topology) charmm_psf =
.rtf (for atom types) charmm_mass_file=
.inp parameter files charmm_parameter_file=
theory=dl_poly : [ list \
list_option=full \
cutoff = [ expr 15 / ] \
scale14 = { } \
atom_types= $types \
atom_charges= $charges \
use_charmm_psf=yes \
charmm_psf_file=4tapap_wat961.psf \
charmm_parameter_file=par_all22_prot_mod.inp \
charmm_mass_file= $top ]

29. Core modules: Geometry Optimisers
Small Molecules
Internal coordinates (delocalised, redundant etc)
Full Hessian
O(N3) cost per step
BFGS, P-RFO
Macromolecules
Cartesian coordinates
Partial Hessian (e.g. diagonal)
O(N) cost per step
Conjugate gradient
L-BFGS
Coupled QM/MM schemes
Combine cartesian and internal coordinates
Reduce cost of manipulating B, G matrices
Define subspace (core region) and relax environment at each step
reduce size of Hessian
exploit greater stability of minimisation vs. TS algorithms
Use approximate scheme for environmental relaxation

30. QUASI - Geometry Optimisation Modules
newopt
A general purpose optimiser
Target functions, specified by function =
copt : cartesian (obsolete)
zopt: z-matrix (now also handles cartesians)
new functions can be written in Tcl (see example rosenbrock)
For QM/MM applications e.g.
P-RFO adapted for presence of soft modes
Hessian update includes partial finite difference in eigenmode basis
New algorithms can be coded in Tcl using primitive steps (forces, updates, steps, etc).
hessian
Generates hessian matrices (e.g. for TS searching)

31. Newopt example - minimisation#
# function zopt allows the newopt optimiser to work with
# the energy as a function of the internal coordinates of
# the molecule
newopt function=zopt : { theory=gamess : { basis=dzp } } \
zmatrix=z

32. Newopt example - transition state determination
# functions zopt.* allow the newopt optimiser to work with
# the energy as a function of the internal coordinates of
# the molecule
set args "{theory=gamess : { basis=3-21g } zmatrix=z}"
hessian function=zopt : [ list $args ] \
hessian=h_fcn_ts method=analytic
newopt function=zopt : [ list $args ] \
method=baker \
input_hessian=h_fcn_ts \
follow_mode=1

33. HDLCopt optimiser hdlcopt
Hybrid Delocalised Internal Coordinate scheme (Alex Turner, Walter Thiel, Salomon Billeter)
Developed within QUASI project
O(N) overall scaling per step
Key elements:
Residue specification, often taken from a pdb file (pdb_to_res) allows separate delocalised coordinates to be generated for each residue
Can perform P-RFO TS search in the first residue with relaxation of the others
increased stability for TS searching
Much smaller Hessians
Further information on algorithm
S.R. Billeter, A.J. Turner and W. Thiel, PCCP 2000, 2, p 2177

34. HDLCopt example # procedure to update the last step
proc hdlcopt_update { args } {
parsearg update { coords } $args
write_xyz coords= $coords file=update.xyz
end_module }
# select residues
set residues [ pdb_to_res "4tapap_wat83.pdb" ]
# load coordinates
read_pdb file=4tapap_wat83.pdb coords=4tapap_wat83.c
hdlcopt coords=4tapap_wat83.c result=4tapap_wat83.opt \
theory=mndo : { hamiltonian=am1 charge=1 optstr={ nprint=2 kitscf=200 } } \
memory=200 residues= $residues \
update_procedure=hdlcopt_update

35. CCP1 QM/MM Optimiser
Developed by Richard Hall (Manchester) as a QM/MM optimisation routine
DLC central residue
CG outer relaxation (e.g. Amber)
Interface exists, but for QM-only optimisation at present.
Not available in the workshop build

36. GULP Interface Simple interface to GULP energy and forces
GULP licensing from Julian Gale
GULP must be compiled in
in alpha version only for the workshop
ChemShell fragment object supports shells
Shells are relaxed by GULP with cores fixed, ChemShell typically controls the core positions
Provide forcefield in standard GULP format

37. GULP interface example
read_input gulp.ff {
# from T.S.Bush, J.D.Gale, C.R.A.Catlow and P.D. Battle
# J. Mater Chem., 4, (1994)
species
Li core
Na core
...
buckingham
Li core O shel
Na core O shel
spring Mg Ca }
add_shells coords=mgo.c symbols= {O Mg}
newopt function=copt : [ list coords=mgo.c theory=gulp : [ list mm_defs=gulp.ff ] ]

38. ChemShell CHARMM Interface
Full functionality from standard academic CHARMM
Dual process model
CHARMM runs a separate process
CHARMM/Tcl interface (CTCL, Alex Turner) uses named pipe to issue CHARMM commands and return results.
commands to export data for DL_POLY and hybrid modules
atomic types and charges
neutral groups
topologies and parameters
Acccess to coupling models internal to CHARMM
GAMESS(US), MOPAC
GAMESS-UK (under development)
collaboration with NIH
explore additional coupling schemes (e.g. double link atom)

39. CHARMM Interface - example
# start charmm process, create chemshell object
# containing the initial structure
charmm.preinit script=charmm.in coords=charmm.c
# ChemShell commands with theory=charmm
hdlcopt theory=charmm coords=charmm.c
# destroy charmm process
charmm.shutdown

40. Molecular Dynamics Module
Design Features
Generic - can integrate QM, MM, QM/MM trajectories
Based on DL_POLY routines
Integration by Verlet leap-frog
SHAKE constraints
Quaternion rigid body motion
NVT, NPT, NVE integration
Script-based control of primitive steps
Simulation Protocols
equilibration
simulated annealing
Tcl access to ChemShell matrix and coordinate objects
e.g. force modification for harmonic restraint
Data output
trajectory output, restart files

41. Molecular Dynamics - arguments
Object oriented syntax follows Tk etc
dynamics dyn1 coords=c … etc
Arguments
theory= module used to compute energy and forces
coords= initial configuration of the system
timestep= integration timestep (ps) [0.0005]
temperature= simulation temperature (K) [293]
mcstep= Max step displacement (a.u.) for Monte Carlo [0.2]
taut= Tau(t) for Berendsen Thermostat (ps) [0.5]
taup= Tau(p) for Berendsen Barostat (ps) [5.0]
compute_pressure= Whether to compute pressure and virial (for NVT simulation)
verbose= Provide additional output
energy_unit= Unit for output

42. Molecular dynamic - arguments
Arguments (cont.)
rigid_groups= rigid group (quaternion defintions)
constraints= interatomic distances for SHAKE
ensemble= Choice of ensemble [NVE]
frozen= List of frozen atoms
trajectory_type= Additional fields for trajectory (> 0 for velocity, > 1 for forces)
trajectory_file= dynamics.trj file for trajectory output
Methods:
Dyn1 configure temperature=300
configure - modify simulation parameters
initvel - initialise random velocities
forces - evaluate molecular forces
step - Take MD step

43. Molecular Dynamics - More methods
update - Request MM or QM/MM pairlist update
mctest - Test step (Monte Carlo only)
output - print data (debugging use only
printe - print step number, kinetic, potential, total energy, temperature, pressure volume and virial.
get - Return a variable from the dynamics,
temperature, input_temperature, pressure, input_pressure, total_energy, kinetic_energy, potential_energy time
trajectory - Output the current configuration to the trajectory file
destroy - free memory and destroy object
fcap - force cap
load - recover positions/velocities
dump - save positions/velocities
dumpdlp - write REVCON

44. Molecular Dynamics - Example
dynamics dyn1 coords=c theory=mndo temperature=300 timestep=0.005 dyn1 initvel set nstep 0
while {$nstep < } {
dyn1 force dyn1 step
# additional Tcl commands here
incr nstep }
dyn1 configure temperature=300
# etc
dyn1 destroy

45. QM Code Interfaces Provides access to third party codes
GAMESS-UK
MOPAC
MNDO
TURBOMOLE
Gaussian98
Standardised interfaces
argument structure
hamiltonian (includes functional)
charge, mult, scftype
basis (internal library or keywords)
accuracy
direct
symmetry
maxcyc...

46. GAMESS-UK Interface Can be built in two ways Notes
Interface calls GAMESS-UK and the job is executed using rungamess (so you may need to have some environment varables set)
parallel execution can be requested even if ChemShell is running serially
GAMESS-UK is built as part of ChemShell
mainly intended for parallel machines
energy coords=c \
theory=gamess : { basis=dzp hamiltonian=b3lyp } \
energy=e
Notes
The jobname is gamess1 unless specified
Some code-specific options
dumpfile= specify dumpfile routing
getq = load vectors from foreign dumpfile

47. GAMESS-UK example - basis library
energy coords=c \
theory=gamess : { basisspec = { { sto-3g *} {dzp o} } } \
energy=e
basisspec has the structure
{ { basis1 atoms-spec1} {basis2 atomspec2} ….. }
Assignment proceeds left to right using pattern matching for atom labels
* is a wild card
This example gives sto-3g for all atoms except o
Library can be extended in the Tcl script (see examples/gamess/explicitbas.chm)
ECPs are used where appropriate for the basis

48. The QM/MM Modelling Approach
Couple quantum mechanics and molecular mechanics approaches
QM treatment of the active site
reacting centre
excited state processes (e.g. spectroscopy)
problem structures (e.g. complex transition metal centre)
Classical MM treatment of environment
enzyme structure
zeolite framework
explicit solvent molecules
bulky organometallic ligands

49. Historical Overview 1976 Warshel, Levitt MM+Semi-empirical
study of Lysozyme
1986 Kollmann, Singh QUEST
ab-initio (Gaussian-80/UCSF) + AMBER
1990 Field, Bash, Karplus CHARMM/AM1
full semi-empirical dynamics implementation
1992 Bernardi, Olivucci, Robb MMVB
simulation on MC-SCF results using VB
1995 van Duijnen, de Vries HONDO/DRF
direct reaction field model of polarisation
1995 Morokuma IMOMM
mechanical embedding with “hidden variable” optimisation
1996 Bakowies and Thiel MNDO/MM
mechanical, electrostatic and polarised semi-empirical models
Eichler, Kölmel, and Sauer QM/Pot
subtractive coupling of GULP/TURBOMOLE

50. Hybrid Module All control data held in Tcl lists created Implements
by setup program (Z-matrix style input)
by scripts or GUI etc
from user-supplied list of QM atoms provided as an argument
Implements
Book-keeping
Division of atom lists
addition of link atoms
summation of energy/forces
Charge shift, and addition of a compensating dipole at M2
Force resolution when link atoms are constrained to bond directions, e.g. the force on first layer MM atom (M1) arising from the force on the link atom is evaluated:
Uses neutral group cutoff for QM/MM interactions

51. Hybrid Module Typical input options qm_theory= mm_theory=
qm_region = { } list of atoms in the QM region
coupling = type of coupling
groups = { } neutral charge groups
cutoff = QM/MM cutoff
atom_charges = MM charges

52. Hybrid Computational Schemes
QM/MM Couplings
Unpolarised
QM polarisation
choice of charges?
MM polarisation
shell model
dipole polarisabilities M2 Q2 M1 L Q1 M2 Q2
Termination Atoms
Chemical type
hydrogen atoms, pseudopotentials adjusted connection atoms, localised orbitals
Charge perturbations
none, charge deletion, charge shift, selection of 1e integrals, double link atoms
Total Energy Expression
Uncorrected
E(M,MM) + E(QL,QM)
Boundary corrected
E(M,MM) + E(QL,QM) - E(L,MM)
Subtractive
E(MQ,MM) + E(QL,QM) - E(QL,MM)

53. Termination of the QM region
Boundary region approaches
Boundary atoms are present in both QM and MM calculations
Range of representations within QM code
Modified ab-initio atom with model potential
Semi-empirical parameterisation
Frozen orbitals
Re-parameterised MM potentials
Link atom schemes
Terminating (link) atoms are invisible to MM calculations
Hydrogen, pseudo-halogen, etc.

54. Conventional QM/MM Scheme
Termination
hydrogen, adjusted connection atom, pseudo-halogen
Coupling
Unpolarised
QM polarisation
MM Polarisation (Direct Reaction Field)
Energy Expression
No correction (Q2-Q1-L force constant mimics Q2-Q1-M1)
MM Charge Adjustments
Deletion (first charge group)
Shift (M1->M2)
Integral selection (semi-empirical)
Advantages
Robust
Disadvantages
charge perturbation at boundary
Applications
zeolites
enzymes

55. Subtractive QM/MM Coupling
Energy Expression
E(MQ,MM) + E(QL,QM) - E(QL,MM)
includes boundary correction
can treat polarisation of both the MM and QM regions at the force-field level
Termination
Any (provided a force field model for QL is available)
Advantages
Potentially highly accurate (free from artefacts)
Can also be used for QM/QM schemes (e.g. IMOMO, Morokuma et al)
Disadvantages
Need for accurate forcefields
Possible catastrophies on potential energy surface
No electrostatic influence on QM wavefunction
Applications
Zeolites (Sauer et al)
under development, theory=subtractive

56. QM/MM Non-bonded Interactions
Short-range forces (van der Waals)
Typically will follow MM conventions (pair potentials etc), sometimes reparameterisation is performed to reflect replacement of point charges interactions with QM/MM electrostatic terms.
Electrostatic interactions:
Mechanical Embedding
in vacuo QM calculation coupled classically to MM via point charges at QM nuclear sites
Electrostatic Embedding
MM atoms appear as centres generating electrostatic contribution to QM Hamiltonian
Polarised Embedding
MM polarisability is coupled to QM charge density

57. Mechanical Embedding Advantages Drawbacks Examples
MM and QM energies are separable
separate MM relaxation, annealing etc possible
QM/MM terms can be integrated directly into the forcefield
No interactions between link atoms and MM centres
QM energies, gradient, Hessian are the same cost as gas phase
Drawbacks
No model for polarisation of QM region
QM/MM electrostatic coupling requires atomic charges for QM atoms
generally these will be dependent on reaction coordinate
Examples
IMOMM (Morokuma)
MNDO/MM (Bakowies and Thiel)

58. Electrostatic Embedding
(i) Assign MM Charges for pure MM system
Derived from empirical schemes (e.g. as part of forcefield)
Fitted to electrostatic potentials
Formal charges (e.g. shell model potentials)
Electronegativity equalisation (e.g. QEq)
(ii) Delete MM charges on atoms in inner region
Attempt to ensure that MM “defect” + terminated QM region has
correct total charge
approximately correct dipole moment
(iii) Insert charges on MM centres into QM Hamiltonian
Explicit point charges
Smeared point charges
Semi-empirical core interaction terms
Make adjustments to closest charges (deletion, shift etc)

59. Creation of neutral embedding site (i) Neutral charge groups
Deletion according to force-field neutral charge-group definitions

60. Creation of neutral embedding site (i) Neutral charge groups
Total charge conserved, poor dipole moments

61. Creation of neutral embedding site (ii) Polar forcefields
O-x
O-x
Si+2x
O-x
O-x
bond dipole models, e.g. for zeolites (Si +0.5x, O -0.5x)

62. Creation of neutral embedding site (ii) Polar forcefields
O-0.5x H
O-0.5x H Si H
O-0.5x H
O-0.5x
Select with dipole_adjust=yes

63. Creation of neutral embedding site (iii) Double link atomsH C C N N C C H R O
Suggestion from Brooks (NIH) for general deletion (not on a force-field neutral charge-group boundary)

64. Creation of neutral embedding site (iii) Double link atomsH C H C H C N H H N C R H O
All fragments are common chemical entities, automatic charge assignment is possible.

65. Boundary adjustments Q2 M2 M1 L Q1 M2 Q2 M3 Q3
Some of the classical centres will lie close to link atom (L)
Artefacts can result if charge at the M1 centre is included in Hamiltonian, many adjustment schemes have been suggested
Adjustments to polarising field can be made independently from specification of MM…MM interactions
Similar adjustments may are needed if M1 is classified as a boundary atom, depending on M1 treatment. Q2 M2 M1 L Q1 M2 Q2 M3 Q3

66. Boundary Adjustments (i) Selective deletion of 1e integrals
L1: Delete integrals for which basis functions i or j are sited on the link atom L
found to be effective for semi-empirical wavefunctions
difference in potential acting on nearby basis functions causes unphysical polarisation for ab-initio QM models
use coupling=L1 with qm_theory=mndo
L3: Delete integrals for which basis functions i and j are cited on the link atom and qA is the neighbouring MM atom (M1)
less consistent results observed in practice †
† Classification from Antes and Thiel, in Combined Quantum Mechanical and Molecular Mechanical Methods, J. Gao and M. Thompson, eds. ACS Symp. Ser., Washington DC, 1998.

67. Boundary Adjustments (ii) Deletion of first neutral charge group
L2 - Exclude charges on all atoms in the neutral group containing M1
Maintains correct MM charge
leading error is the missing dipole moment of the first charge group
Generally reliable
free from artefacts arising from close contacts
Limitations
only applicable in neutral group case (e.g. AMBER, CHARMM)
neutral groups are highly forcefield dependent
problematic if a charge group needs to be split
Application
biomolecular systems
use coupling=L2 with groups = { … }

68. Boundary adjustments (iii) Charge shift
Delete charge on M1
Add an equal fraction of q(M1) to all atoms M2
Add correcting dipole to M2 sites (implemented as a pair of charges)
charge and dipole of classical system preserved
Leading sources of residual error is that Q---L dipole moment is not equivalent to Q------M
Requested using coupling=shift Q2 M2 M1 L Q1 M2 Q2 M3 Q3

69. Boundary adjustments (iv) Gaussian Blur
Delocalise point charge using Gaussian shape function
Large Gaussian width : electrostatic coupling disappears
Narrow Gaussian width : recover point charge behaviour
Intermediate values
short range interactions are attenuated
long range electrostatics are preserved
Importance of balance - apply to entire MM system or to first neutral group
Particularly valuable for double-link atom scheme where MM link atom charge lies within QM molecular envelope

70. Gaussian Blur: QM/MM EthaneC H H C H H H MM QM
Aggregate dipole moment, with MM atoms broadened
Large Gaussian width dipole converges to that of the QM methane ( 0 )
Small Gaussian width point charges polarise the QM region, away from the C-H bond
Compare with dipole of MM methyl group (0.18)

71. Electrostatic Embedding Summary
Advantages
Capable of treating changes in charge density of QM
important for solvation energies etc
No need for a charge model of QM region
can readily model reactions that involve charge separation
Drawbacks
Charges must provide a reliable model of electrostatics
reparameterisation may be needed for some forcefields
Danger of spurious interactions between link atoms and charges
QM evaluation needed to obtain accurate MM forces
QM energy, gradient, Hessian are more costly than gas phase QM

72. 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 MM QM
Advantages
suitable for ionic materials
Disadvantages
require specialised pseudopotentials
Applications
metal oxide surfaces

73. GULP - GAMESS-UK coupling
Features
From Julian Gale (Imperial College), classical energies including shell model
Self-consistent coupling of shell relaxation to GAMESS-UK
Import electrostatic forces on shells from GAMESS-UK
relax shell positions
Defect energies (Mott Littleton scheme) a posteriori
MPI parallel version available.
Use coupling=shift (without any bonds, and with some shells in MM region, include_qm_force=yes for GULP
ChemShell - hybrid module
GAMESS-UK SCF & shell forces
GULP shell relaxation
GAMESS-UK atomic forces
GULP forces

74. The Cerius-2 GUI
Provides control of QM, MM, and QM/MM calculations using HDLCOpt, Newopt, and Dynamics modules
Writes a ChemShell script comprising
control parameters
job-specific segments
To set up a new system, execute
% make_run_dir
first to create cerius-2 files and link some ChemShell template scripts
See /workshop/examples/chemsh/SDK & manual

75. Example files
SDK/
SUMMARY
charmm/
chemgui/
dl_poly/
dynamics/
field/
force/
fragment/
gamess/
gaussian/
gulp/
hdlcopt/
hybrid/
irc/
matrix/
mndo/
mopac/
newopt/
newopt_alex/
parallel/
quasi/
surface/
turbomole/
xtal/
zmatrix/