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# sccdftb (c47b2)

Combined Quantum Mechanical and Molecular Mechanics Method

Based on SCCDFTB in CHARMM

by Qiang Cui and Marcus Elstner

(cui@chem.wisc.edu, elstner@phys.upb.de)

The approximate Density Functional program SCCDFTB (Self-

consistent charge Density-Functional Tight-Binding) is interfaced with

This method is described in

Phys. Rev. B, 58,7260 (1998)

Phys. Stat. Sol. B, 217, 357 (2000)

J. Phys. : Condens. Matter., 14, 3015 (2002)

Recent reviews are:

WIREs Comput. Mol. Sci., 4, 49-61 (2014)

PCCP, 16, 14368-14377 (2014)

The QM/MM interface in CHARMM has been described in

J. Phys. Chem. B 105 (2001) 569

The GHO-SCC-DFTB/MM boundary treatment has been described

in J. Phys. Chem. A 108 (2004) 5454.

A recent review of SCC-DFTB/MM can be found in

J. Phys. Chem. B. 110, 6458-6469 (2006). Recent extensions can be found in

J. Phys. Chem. A. 111, 10861-10873 (2007).

J. Chem. Theory Comput. 7, 931-948 (2011).

The extension of the SCC-DFTB method to work with the Replica Path

and the Nudged Elastic Band methods has been described in the following

paper and should be cited when applied:

H. L. Woodcock, M. Hodoscek, and B. R. Brooks Exploring SCC-DFTB Paths

for Mapping QM/MM Reaction Mechanisms J. Phys. Chem. A; 2007; 111(26)

5720-5728.

* Description | Description of the sccdftb commands.

* Usage | How to run sccdftb in CHARMM.

* Installation | How to install sccdftb in CHARMM environment.

* FEP | Free energy perturbations with SCC-DFTB/MM

* Electrostatics | Electrostatics in SCC-DFTB/MM

* GLNK | GLNK Commands

* Status | Status of the interface code.

Based on SCCDFTB in CHARMM

by Qiang Cui and Marcus Elstner

(cui@chem.wisc.edu, elstner@phys.upb.de)

The approximate Density Functional program SCCDFTB (Self-

consistent charge Density-Functional Tight-Binding) is interfaced with

This method is described in

Phys. Rev. B, 58,7260 (1998)

Phys. Stat. Sol. B, 217, 357 (2000)

J. Phys. : Condens. Matter., 14, 3015 (2002)

Recent reviews are:

WIREs Comput. Mol. Sci., 4, 49-61 (2014)

PCCP, 16, 14368-14377 (2014)

The QM/MM interface in CHARMM has been described in

J. Phys. Chem. B 105 (2001) 569

The GHO-SCC-DFTB/MM boundary treatment has been described

in J. Phys. Chem. A 108 (2004) 5454.

A recent review of SCC-DFTB/MM can be found in

J. Phys. Chem. B. 110, 6458-6469 (2006). Recent extensions can be found in

J. Phys. Chem. A. 111, 10861-10873 (2007).

J. Chem. Theory Comput. 7, 931-948 (2011).

The extension of the SCC-DFTB method to work with the Replica Path

and the Nudged Elastic Band methods has been described in the following

paper and should be cited when applied:

H. L. Woodcock, M. Hodoscek, and B. R. Brooks Exploring SCC-DFTB Paths

for Mapping QM/MM Reaction Mechanisms J. Phys. Chem. A; 2007; 111(26)

5720-5728.

* Description | Description of the sccdftb commands.

* Usage | How to run sccdftb in CHARMM.

* Installation | How to install sccdftb in CHARMM environment.

* FEP | Free energy perturbations with SCC-DFTB/MM

* Electrostatics | Electrostatics in SCC-DFTB/MM

* GLNK | GLNK Commands

* Status | Status of the interface code.

Top

Note: before running CHARMM with SCCDFTB enabled, it may be necessary

to execute the following at the command line.

ulimit -s unlimited

Failure to do so may result in unexpected segfaults.

The SCCDFTB QM potential is initialized with the SCCDFTB command

[SYNTAX SCCDFTB]

SCCDFTB [REMOve] [CHRG] (atom selection) [GLNK atom-selection]

[TEMPerature] [SCFtolerance]

[CUTF] [EWAD EOPT KAPPA kappa KMAX kmax KSQMAX ksqmax]

[PMEW FFTX fftx FFTY ffty FFTZ fftz ORDEr order]

[UPDT 0]

[MULL]

[DISP]

[HBON GAUS]

[DHUB DHGA]

[D3RD]

[SCFC]

[QDIP UDIP unit]

[SHES] [RHES]

[CDKO]

[UNPE unpe]

[LDEP]

[DMEThod int]

[MIXE int] [GENS int] [SYMM real]

[IGUESS]

[IDAMP]

[PLUS]

[NBO]

[PERT TEMP SCFT CHRG (atom selection)]

REMOve: Classical energies within QM atoms are removed.

CHRG: Net charge in the QM subsystem.

The atoms in selection will be treated as QM atoms.

GLNK atom-selection: contains a list of atoms that are selected as

GHO boundary atoms.

TEMPerature: Specifies the electronic temperature (Fermi distribution).

Can be used to accelerate or achieve SCF convergence

(default =0.0).

SCFtolerance: Convergence criteria for the SCF cycle. As default

a value of 1.d-7 is used.

CUTF: a flag that turns on cut-off, will use the same scheme used for

MM interactions (allows atom-based fshift and shift). This option

is recommended for QM-MM interactions in EWAD calculation.

EWAD: a flag that turns on ewald summation for QM-QM and QM-MM

electrostatic interactions

EOPT: performs an internal optimization for kappa and kmax as well as

real-space sum. NOT recommended - very inefficient. incompatible

with CUTF

KAPPA, KMAX, KSQMAX: parameters used for QM-QM and QM-MM ewald

contributions.

PMEW: a flag that turns on particle mesh ewald (PME) summation for

QM-QM and QM-MM electrostatic interactions

FFTX, FFTY, FFTZ: Integer numbers of Fast Fourier Transform grid points

for the charge mesh (default 32)

ORDEr: specifies the order of the B-spline interpolation, e.g. cubic is

order 4, fifth degree is ORDEr 6 (default). The ORDEr must be

an even number and at least 4.

UPDT: Whether to update the box during a MD run. Default is 0 (not update!)

Do NOT forget to specify this to 1 when running CPT calculations

(although additional tests should be done for CPT in terms of virial

calculations!)

MULL: Transfer the mulliken charges to the CG array such that they can be

printed out by transferring the CG array to any vectors (e.g.,

scalar wmain = charge; print coor)

DISP: Dispersion interactions among QM atoms can be calculated using an

empirical formular (Elstner et al. J. Chem. Phys. 114, 5149, 2001).

One needs to specify a set of parameters in the DISPERSION.INP file

(see the above ref for details).

TWOBody THREebody: Add the D3(BJ) two-body or three-body dispersion correction

due to Grimme (Grimme et al. J. Chem. Phys. 132 (2010), 154104 and Grimme

et al. J. Comput. Chem. 32 (2011), 1456-1465). Parameters are set

automatically with the DFTB method (I.e. DFTB2/DFTB3/CPE correction, etc).

HBON: The short-range behavior of XH gamma function is modified with a damping

function. This significantly enhances the hydrogen bonding interactions

(Elstner, Cui, unpublished). The damping exponent needs to be specified

in the sccdftb.dat file. However, with the modified gamma, the repulsive

potential has to be adjusted accordingly. This can be done in an

empirical fashion by including a Gaussian (constrained to operate in

a range by a switching function) in the relevant repulsive potential;

the parameters for the Gaussian and the switching function need to be

specified in the spl file and turned on using the GAUS keyword.

DHUB: --> obsolete keyword (but still fully functional): use D3RD instead.

To improve proton affinities, which depend much on the charges in the

protonated DHGA and deprotonated molecules, the SCC-DFTB is expanded

to the 3rd order. Currently only on-site terms have been included,

which were observed to have a major impact on the calculated PAs for

many molecules. The relevant parameters are the derivative of the

Hubbard parameters (related to chemical hardness), which need to be

specified in the sccdftb.dat file. The DHGA keyword includes further

flexibility in the behavior of the Hubbard parameters as a function of

charge (Elstner, Cui, JPC-A, 111, 10861-10873 (2007)).

D3RD: Full 3rd order extension of SCC-DFTB. For invoking DFTB3

(JCTC 2011,7,931) D3RD should be used in combination with HBON.

The necessary parameters (Hubbard derivatives) need to be

specified in the sccdftb.dat file (see below).

SCFC: instead of using energy difference between iterations to determine SCF

convergence, use difference in Mulliken charge between iterations. The

threshold is 0.05*sqrt(SCFtolerance). This option can be useful when

very tight convergence is desired (see, e.g., SI of JCP, 127, 234504

(2007))

CPE0, CPEQ: Use the charge-independent DFTB3/CPE model with the parameters

from Christensen et al. (2015) http://arxiv.org/abs/1507.00370 - Note:

The parameters are optimized for simultaneous use of the D3(BJ)

three-body dispersion correction (i.e., the THREebody keyword).

Note: the CPE methods requires CHARMM to be compiled with the +DFTBMKL

option - this is described under the MIXE keyword in this document.

QDIP: indicate that QM dipole moment will be written to file of unit # UDIP.

Can be useful for IR calculations using ACF of QM dipoles.

SHES: Save "dd1.dat" file in finite differences frequency calculations

(DIAG FINITE and REDU FIX FINITE)

RHES: Read in "dd1.dat" file (from parent directory of the calculation)

CDKO: The Charge-Dependent Klopman-Ohno flag activates a short-range

damping of the 1/r electrostatic interaction between QM (SCC-DFTB)

and MM atoms taking into account charge-penetration effects. It

is particularly useful for describing highly charged species in

a QM/MM setup such as phosphate hydrolysis reactions in

biological systems and was investigated in combination with

an optimized set of element type dependent QM Van der Waals

parameters (Hou, Cui, JCTC, 8, 4293-4304 (2012)). The relevant parameters

need to be specified in a separate input file named ko_para.inp

(see below for details) that needs to be located in the directory

where CHARMM is executed (similar to sccdftb.dat). Note, when

using in combination with LDEP the s-orbital Hubbard (and deriv)

is taken as the QM Hubbard for the QM/MM interaction.

UNPE: Followed by a floating-point number this flag specifies the

number of unpaired electrons and invokes the inclusion of

spin-polarization effects in a collinear description (see e.g.

JPC-A 2007,111,5622. and refs therein).

LDEP: L-dependence of the Hubbard parameters. This option should only be

used with DFTB parameters that are designed for l-dependence! If

D3RD is switched on also the Hubbard derivative parameters for s-,

p-, and d-orbitals are necessary and need to be specified in the

sccdftb.dat (see below). An example for this option is provided

in test/c38test/sccdftb_ldep.inp.

DMET: Needs an integer(0/1/2/3) as input to specify the diagonalizer for solving

the secular equations in DFTB.

0 : Legacy diagonalizer

1 : LAPACK DSYGV, requires +DFTBMKL

2 : LAPACK DSYGVD, requires +DFTBMKL - (recommended)

Options 1 and 2 requires CHARMM to be linked to an implementation of LAPACK,

and to be compiled with the +DFTBMKL option. If +DFTBMKL is used, BLAS routines

are used to calculate the density matrix and calculate the Mulliken charges and

DFTB gradient. DMET 2 is usually the fastest, and will normally speed up the

DFTB calculation substantially.

MIXE: Needs an integer(0/1/2/3) as input to specify the charge-mixing scheme

to be used in the SCF iterations.

0 : Simple mixing scheme

1 : Anderson mixing scheme (recommended)

2 : Broyden mixing scheme (default)

3 : DIIS mixing scheme

For the Anderson and DIIS mixing schemes, the LAPACK subroutine DGESV

is required. Hence the CHARMM executable has to be linked to LAPACK

(Intel MKL is recommended). For the Anderson and DIIS implementation to

work, the following need to be done:

Add DFTBMKL to the installation command line such that DFTBMKL gets

included in the generated pref.dat. For example:

./configure --with-sccdftb --add dftbmkl

make -C build/cmake install

If MIXE is specified as '1' or '3' in the input without having compiled CHARMM

with LAPACK, the Broyden mixer will be used instead of Anderson/DIIS.

In situations where Intel MKL is unavailable, simply compile with the OS

default version of BLAS and LAPACK by linking CHARMM with:

-llapack -lblas

For example, one may set the environment variable LDFLAGS to the above

before executing the configure script.

Note that Intel MKL is usually the fastest LAPACK implementation for CHARMM.

GENS: Number of iterations (including the current one) whose input and output

charges are mixed in the Anderson mixing scheme. Generally, 5-6 should be

sufficient. Default: 8

SYMM: A real number, in order to avoid linear dependency near the convergence

region in the Anderson mixing scheme. Default: 0.01 (recommended)

IGUESS: Order of DXL-BOMD algorithm for charge propagation from previous

dynamics. The input value and real order correspondence is [ 105: 1,

107: 3, 109: 5, 111: 7, 113: 9, 115: 11, 117: 13].

The details of the algorithm can be found in J. Chem. Phys. (135,

044122, 2011). The default value is 0, which means getting charge from

the previous geometry converged values.

IDAMP: Number of damping steps in DXL-BOMD. The number of steps before turning

on DXL-BOMD algorithm.

PLUS: Use the libDFTB+ back-end to carry out the SCC-DFTB calculations. This

option requires CHARMM to be compiled with the +DFTBPLUS option.

Instructions for this can be found in the installation section in this

document.

NBO: CHARMM will output the nbo.47 file that can be read in by NBO 6.0 to conduct

Natural Bonding Orbital (NBO) analysis of the bonding structure.

PERT: With the PERT keyword within the SCCDFTB command, alchemical free energy

simulation is conducted between two atomic selections, each with its own

TEMP SCFT and CHRG variables. [Currently open-shell cases not considered]

This is used to convert the QM region into a combination of QM/MM atoms;

coupled with a thermodynamic cycle, this allows solvation free energy

and ligand binding calculations. See, for example, X. Lu et al., Mol. Siml.

42, 1056-1078 (2016).

Note that when converting the entire QM region into MM atoms, no PERT keyword

is needed in the SCCDFTB module. For some examples, see the section in

pert.info.

In the SCCDFTB program the atomtypes are represented by consecutive

numbers. The definition of SCCDFTB atom numbers has to be accomplished

before invoking the SCCDFTB command. The numbers are stored in WMAIN.

If the QM system e.g contains only O, N, C and H atoms,

the the numbering can be executed as follows:

scalar WMAIN set 1.0 sele type O* SHOW end

scalar WMAIN set 2.0 sele type N* SHOW end

scalar WMAIN set 3.0 sele type C* SHOW end

scalar WMAIN set 4.0 sele type H* SHOW end

Now, the O atoms are represented by 1.0, the N atoms by 2.0 etc.

Link atom may be added between an QM and MM atoms with the

following command:

ADDLinkatom link-atom-name QM-atom-spec MM-atom-spec

link-atom-name ::= a four character descriptor starting with QQ.

atom-spec::= {residue-number atom-name}

{ segid resid atom-name }

{ BYNUm atom-number }

When using link atoms to break a bond between QM and MM

regions bond and angle parameters have to be added to parameter file

or better use READ PARAm APPEnd command.

If define is used for selection of QM region put it after all

ADDLink commands so the numbers of atoms in the selections are not

changed. Link atoms are always selected as QM atoms.

Currently, three different link atom schemes are implemented.

SLA(default), EXGR and DIV. For a detailed comparison between them, see

J. Phys. Chem. B 109, 9082-9095 (2005). Briefly, SLA should be avoided

if there is major charge change during the QM/MM calculations (e.g.,

deprotonation). EXGR in general works well, but can be problematic if the

QM region interacts directly with the mainchain NH (in the same group as

CA and therefore can be excluded from interacting with QM).

Example:

SCCDFTB DIV remove CHRG 2 SELE resn @m END TEMP 0.00 SCFT 0.00000001

Note: before running CHARMM with SCCDFTB enabled, it may be necessary

to execute the following at the command line.

ulimit -s unlimited

Failure to do so may result in unexpected segfaults.

The SCCDFTB QM potential is initialized with the SCCDFTB command

[SYNTAX SCCDFTB]

SCCDFTB [REMOve] [CHRG] (atom selection) [GLNK atom-selection]

[TEMPerature] [SCFtolerance]

[CUTF] [EWAD EOPT KAPPA kappa KMAX kmax KSQMAX ksqmax]

[PMEW FFTX fftx FFTY ffty FFTZ fftz ORDEr order]

[UPDT 0]

[MULL]

[DISP]

[HBON GAUS]

[DHUB DHGA]

[D3RD]

[SCFC]

[QDIP UDIP unit]

[SHES] [RHES]

[CDKO]

[UNPE unpe]

[LDEP]

[DMEThod int]

[MIXE int] [GENS int] [SYMM real]

[IGUESS]

[IDAMP]

[PLUS]

[NBO]

[PERT TEMP SCFT CHRG (atom selection)]

REMOve: Classical energies within QM atoms are removed.

CHRG: Net charge in the QM subsystem.

The atoms in selection will be treated as QM atoms.

GLNK atom-selection: contains a list of atoms that are selected as

GHO boundary atoms.

TEMPerature: Specifies the electronic temperature (Fermi distribution).

Can be used to accelerate or achieve SCF convergence

(default =0.0).

SCFtolerance: Convergence criteria for the SCF cycle. As default

a value of 1.d-7 is used.

CUTF: a flag that turns on cut-off, will use the same scheme used for

MM interactions (allows atom-based fshift and shift). This option

is recommended for QM-MM interactions in EWAD calculation.

EWAD: a flag that turns on ewald summation for QM-QM and QM-MM

electrostatic interactions

EOPT: performs an internal optimization for kappa and kmax as well as

real-space sum. NOT recommended - very inefficient. incompatible

with CUTF

KAPPA, KMAX, KSQMAX: parameters used for QM-QM and QM-MM ewald

contributions.

PMEW: a flag that turns on particle mesh ewald (PME) summation for

QM-QM and QM-MM electrostatic interactions

FFTX, FFTY, FFTZ: Integer numbers of Fast Fourier Transform grid points

for the charge mesh (default 32)

ORDEr: specifies the order of the B-spline interpolation, e.g. cubic is

order 4, fifth degree is ORDEr 6 (default). The ORDEr must be

an even number and at least 4.

UPDT: Whether to update the box during a MD run. Default is 0 (not update!)

Do NOT forget to specify this to 1 when running CPT calculations

(although additional tests should be done for CPT in terms of virial

calculations!)

MULL: Transfer the mulliken charges to the CG array such that they can be

printed out by transferring the CG array to any vectors (e.g.,

scalar wmain = charge; print coor)

DISP: Dispersion interactions among QM atoms can be calculated using an

empirical formular (Elstner et al. J. Chem. Phys. 114, 5149, 2001).

One needs to specify a set of parameters in the DISPERSION.INP file

(see the above ref for details).

TWOBody THREebody: Add the D3(BJ) two-body or three-body dispersion correction

due to Grimme (Grimme et al. J. Chem. Phys. 132 (2010), 154104 and Grimme

et al. J. Comput. Chem. 32 (2011), 1456-1465). Parameters are set

automatically with the DFTB method (I.e. DFTB2/DFTB3/CPE correction, etc).

HBON: The short-range behavior of XH gamma function is modified with a damping

function. This significantly enhances the hydrogen bonding interactions

(Elstner, Cui, unpublished). The damping exponent needs to be specified

in the sccdftb.dat file. However, with the modified gamma, the repulsive

potential has to be adjusted accordingly. This can be done in an

empirical fashion by including a Gaussian (constrained to operate in

a range by a switching function) in the relevant repulsive potential;

the parameters for the Gaussian and the switching function need to be

specified in the spl file and turned on using the GAUS keyword.

DHUB: --> obsolete keyword (but still fully functional): use D3RD instead.

To improve proton affinities, which depend much on the charges in the

protonated DHGA and deprotonated molecules, the SCC-DFTB is expanded

to the 3rd order. Currently only on-site terms have been included,

which were observed to have a major impact on the calculated PAs for

many molecules. The relevant parameters are the derivative of the

Hubbard parameters (related to chemical hardness), which need to be

specified in the sccdftb.dat file. The DHGA keyword includes further

flexibility in the behavior of the Hubbard parameters as a function of

charge (Elstner, Cui, JPC-A, 111, 10861-10873 (2007)).

D3RD: Full 3rd order extension of SCC-DFTB. For invoking DFTB3

(JCTC 2011,7,931) D3RD should be used in combination with HBON.

The necessary parameters (Hubbard derivatives) need to be

specified in the sccdftb.dat file (see below).

SCFC: instead of using energy difference between iterations to determine SCF

convergence, use difference in Mulliken charge between iterations. The

threshold is 0.05*sqrt(SCFtolerance). This option can be useful when

very tight convergence is desired (see, e.g., SI of JCP, 127, 234504

(2007))

CPE0, CPEQ: Use the charge-independent DFTB3/CPE model with the parameters

from Christensen et al. (2015) http://arxiv.org/abs/1507.00370 - Note:

The parameters are optimized for simultaneous use of the D3(BJ)

three-body dispersion correction (i.e., the THREebody keyword).

Note: the CPE methods requires CHARMM to be compiled with the +DFTBMKL

option - this is described under the MIXE keyword in this document.

QDIP: indicate that QM dipole moment will be written to file of unit # UDIP.

Can be useful for IR calculations using ACF of QM dipoles.

SHES: Save "dd1.dat" file in finite differences frequency calculations

(DIAG FINITE and REDU FIX FINITE)

RHES: Read in "dd1.dat" file (from parent directory of the calculation)

CDKO: The Charge-Dependent Klopman-Ohno flag activates a short-range

damping of the 1/r electrostatic interaction between QM (SCC-DFTB)

and MM atoms taking into account charge-penetration effects. It

is particularly useful for describing highly charged species in

a QM/MM setup such as phosphate hydrolysis reactions in

biological systems and was investigated in combination with

an optimized set of element type dependent QM Van der Waals

parameters (Hou, Cui, JCTC, 8, 4293-4304 (2012)). The relevant parameters

need to be specified in a separate input file named ko_para.inp

(see below for details) that needs to be located in the directory

where CHARMM is executed (similar to sccdftb.dat). Note, when

using in combination with LDEP the s-orbital Hubbard (and deriv)

is taken as the QM Hubbard for the QM/MM interaction.

UNPE: Followed by a floating-point number this flag specifies the

number of unpaired electrons and invokes the inclusion of

spin-polarization effects in a collinear description (see e.g.

JPC-A 2007,111,5622. and refs therein).

LDEP: L-dependence of the Hubbard parameters. This option should only be

used with DFTB parameters that are designed for l-dependence! If

D3RD is switched on also the Hubbard derivative parameters for s-,

p-, and d-orbitals are necessary and need to be specified in the

sccdftb.dat (see below). An example for this option is provided

in test/c38test/sccdftb_ldep.inp.

DMET: Needs an integer(0/1/2/3) as input to specify the diagonalizer for solving

the secular equations in DFTB.

0 : Legacy diagonalizer

1 : LAPACK DSYGV, requires +DFTBMKL

2 : LAPACK DSYGVD, requires +DFTBMKL - (recommended)

Options 1 and 2 requires CHARMM to be linked to an implementation of LAPACK,

and to be compiled with the +DFTBMKL option. If +DFTBMKL is used, BLAS routines

are used to calculate the density matrix and calculate the Mulliken charges and

DFTB gradient. DMET 2 is usually the fastest, and will normally speed up the

DFTB calculation substantially.

MIXE: Needs an integer(0/1/2/3) as input to specify the charge-mixing scheme

to be used in the SCF iterations.

0 : Simple mixing scheme

1 : Anderson mixing scheme (recommended)

2 : Broyden mixing scheme (default)

3 : DIIS mixing scheme

For the Anderson and DIIS mixing schemes, the LAPACK subroutine DGESV

is required. Hence the CHARMM executable has to be linked to LAPACK

(Intel MKL is recommended). For the Anderson and DIIS implementation to

work, the following need to be done:

Add DFTBMKL to the installation command line such that DFTBMKL gets

included in the generated pref.dat. For example:

./configure --with-sccdftb --add dftbmkl

make -C build/cmake install

If MIXE is specified as '1' or '3' in the input without having compiled CHARMM

with LAPACK, the Broyden mixer will be used instead of Anderson/DIIS.

In situations where Intel MKL is unavailable, simply compile with the OS

default version of BLAS and LAPACK by linking CHARMM with:

-llapack -lblas

For example, one may set the environment variable LDFLAGS to the above

before executing the configure script.

Note that Intel MKL is usually the fastest LAPACK implementation for CHARMM.

GENS: Number of iterations (including the current one) whose input and output

charges are mixed in the Anderson mixing scheme. Generally, 5-6 should be

sufficient. Default: 8

SYMM: A real number, in order to avoid linear dependency near the convergence

region in the Anderson mixing scheme. Default: 0.01 (recommended)

IGUESS: Order of DXL-BOMD algorithm for charge propagation from previous

dynamics. The input value and real order correspondence is [ 105: 1,

107: 3, 109: 5, 111: 7, 113: 9, 115: 11, 117: 13].

The details of the algorithm can be found in J. Chem. Phys. (135,

044122, 2011). The default value is 0, which means getting charge from

the previous geometry converged values.

IDAMP: Number of damping steps in DXL-BOMD. The number of steps before turning

on DXL-BOMD algorithm.

PLUS: Use the libDFTB+ back-end to carry out the SCC-DFTB calculations. This

option requires CHARMM to be compiled with the +DFTBPLUS option.

Instructions for this can be found in the installation section in this

document.

NBO: CHARMM will output the nbo.47 file that can be read in by NBO 6.0 to conduct

Natural Bonding Orbital (NBO) analysis of the bonding structure.

PERT: With the PERT keyword within the SCCDFTB command, alchemical free energy

simulation is conducted between two atomic selections, each with its own

TEMP SCFT and CHRG variables. [Currently open-shell cases not considered]

This is used to convert the QM region into a combination of QM/MM atoms;

coupled with a thermodynamic cycle, this allows solvation free energy

and ligand binding calculations. See, for example, X. Lu et al., Mol. Siml.

42, 1056-1078 (2016).

Note that when converting the entire QM region into MM atoms, no PERT keyword

is needed in the SCCDFTB module. For some examples, see the section in

pert.info.

In the SCCDFTB program the atomtypes are represented by consecutive

numbers. The definition of SCCDFTB atom numbers has to be accomplished

before invoking the SCCDFTB command. The numbers are stored in WMAIN.

If the QM system e.g contains only O, N, C and H atoms,

the the numbering can be executed as follows:

scalar WMAIN set 1.0 sele type O* SHOW end

scalar WMAIN set 2.0 sele type N* SHOW end

scalar WMAIN set 3.0 sele type C* SHOW end

scalar WMAIN set 4.0 sele type H* SHOW end

Now, the O atoms are represented by 1.0, the N atoms by 2.0 etc.

Link atom may be added between an QM and MM atoms with the

following command:

ADDLinkatom link-atom-name QM-atom-spec MM-atom-spec

link-atom-name ::= a four character descriptor starting with QQ.

atom-spec::= {residue-number atom-name}

{ segid resid atom-name }

{ BYNUm atom-number }

When using link atoms to break a bond between QM and MM

regions bond and angle parameters have to be added to parameter file

or better use READ PARAm APPEnd command.

If define is used for selection of QM region put it after all

ADDLink commands so the numbers of atoms in the selections are not

changed. Link atoms are always selected as QM atoms.

Currently, three different link atom schemes are implemented.

SLA(default), EXGR and DIV. For a detailed comparison between them, see

J. Phys. Chem. B 109, 9082-9095 (2005). Briefly, SLA should be avoided

if there is major charge change during the QM/MM calculations (e.g.,

deprotonation). EXGR in general works well, but can be problematic if the

QM region interacts directly with the mainchain NH (in the same group as

CA and therefore can be excluded from interacting with QM).

Example:

SCCDFTB DIV remove CHRG 2 SELE resn @m END TEMP 0.00 SCFT 0.00000001

Top

SCCDFTB input files

-------------------

SCCDFTB needs to read in the parameter files, which have

a two-body character. Therefore, the interaction parmeters

for all pairs of atoms have to be read in.

These files are named like oo.spl, on.spl, oc.spl, no.spl etc.,

where oo.spl contains the two-center integrals for the O-O interaction,

on.spl the two-center integrals for the O-N interaction etc.

DFTB needs these parameters for the O-N and N-O interaction,

similarily for all other pairwise interactions.

The file sccdftb.dat contains the paths to these parameters, as:

'potential:atom-1-atom-1'

'potential:atom-1-atom-2'

'potential:atom-1-atom-3'

... \\

'potential:atom-1-atom-N'

'potential:atom-2-atom-1'

... \\

'potential:atom-2-atom-N'

'potential:atom-N-atom-1'

... \\

'potential:atom-N-atom-N'

where atom-1 is the atom defined by 1.0, as described above,

atom-2 defined in WMAIN by 2.0 etc.

If open-shell treatment via UNPE is specified, SCC-DFTB needs to read

in the spin-polarization constants. These are listed directly after the

parameter files section, one line for each atom type as defined in

WMAIN and following the same order as above (first line for atom-1,

second line for atom-2, and so on). Each line needs to look like:

spin-'dummy' Wss Wsp Wps Wpp Wsd Wpd Wdd Wds Wdp

where for readability 'dummy' can be the name of the atom type (e.g. c

for carbon). Values for the constants Wss,... can be found in the

Dissertation thesis of Christof Koehler, 2003, Unviversity Paderborn,

page 114f, which is also available online via

http://digital.ub.uni-paderborn.de/hs/content/titleinfo/3163

When third order DFTB is invoked via D3RD (or the now obsolete keyword

DHUB) the Hubbard derivatives Ud need to be specified following the

parameter file section, or the spin-section if the UNPE keyword is used:

'dummy' Ud-atom1

'dummy' Ud-atom2

...

For values of Ud see JCTC 2011,7,931.

When D3RD and LDEP is specified the Hubbard derivatives section looks

like:

'dummy' Ud-atom1-d-orbital Ud-atom1-p-orbital Ud-atom1-s-orbital

'dummy' Ud-atom2-d-orbital Ud-atom2-p-orbital Ud-atom2-s-orbital

...

If DHGA is specified (again, this is an obsolete option and was only

used in combination with DHUB), one line containing three number follow

in the form:

v0_hgau alp_hgau q0_hgau

For details see JCTC 2008,4,2067.

For HBON one additional parameter 'zeta' is necessary which is set as a

single number in a single line following all previous sections (if

invoked via corresponding keyword).

An example of a system containing O N C and H and having specified the

keywords UNPE 1.0, D3RD, and HBON, sccdftb.dat would look like:

'PATH/oo.spl'

'PATH/on.spl'

'PATH/oc.spl'

'PATH/oh.spl'

'PATH/no.spl'

'PATH/nn.spl'

'PATH/nc.spl'

'PATH/nh.spl'

'PATH/co.spl'

'PATH/cn.spl'

'PATH/cc.spl'

'PATH/ch.spl'

'PATH/ho.spl'

'PATH/hn.spl'

'PATH/hc.spl'

'PATH/hh.spl'

spin-o -0.035 -0.030 -0.030 -0.028 0.0 0.0 0.0 0.0 0.0

spin-n -0.033 -0.027 -0.027 -0.026 0.0 0.0 0.0 0.0 0.0

spin-c -0.031 -0.025 -0.025 -0.023 0.0 0.0 0.0 0.0 0.0

spin-h -0.072 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0

'o' -0.19

'n' -0.13

'c' -0.23

'h' -0.16

4.2

where PATH specifies the path to the directory where the data files

are located. Be careful, an error in the sequence or a wrong assingnment

of parameters to atoms (coordinates) will make results meaningless.

Parameter files can be downloaded at www.dftb.org or

requested from Marcus Elstner (marcus.elstner@kit.edu).

Another input file is necessary if the CDKO keyword is applied.

It contains two parameters for each QM atom type and one atom-size

describing parameter for each element appearing in the MM part. The

file is called ko_para.inp and needs to look like:

nQMatomtypes nMMelements

WMAIN:atom-1 a:atom-1 b:atom-1

WMAIN:atom-2 a:atom-2 b:atom-2

... ...

WMAIN:nQMatomtypes a:atom-nQMatomtypes b:atom-nQMatomtypes

<blank line>

name:MMelement1 U:MMelement1

name:MMelement2 U:MMelement2

... ...

name:nMMelements U:nMMelements

For the sccdftb.dat example above, the number of QM atomtypes is

nQMatomtypes = 4 (O,N,C, and H), if the MM part is composed solely out

of water the number of MM elements nMMelements = 2, where

name:MMelement1 is O and name:MMelement2 is H. a, b, and U are the

corresponding parameters published for phosphate

hydrolysis reactions (Hou, Cui, 8, 4293-4304 (2012)).

An example for this scheme is provided in test/c37test/sccdftb_cdko.inp

For additional discussion on the CDKO parameters, see, JPC, B 118, 11007-11027 (2014).

SCCDFTB output files (currently disabled)

-----------------------------------------

SPE.DAT : contains the Kohn-Sham energies with occupations numbers.

CHR.DAT : contains the atomic (Mulliken) charges of the atoms

(first row) and for the orbitals (s, px,py,pz,dxx.. ) in the

following columns.

REST.DAT: contains dipolemoment (D), calculated from the Mulliken

charges (not a reliable estimate of Dipolemoment in general!)

SCCDFTB input files

-------------------

SCCDFTB needs to read in the parameter files, which have

a two-body character. Therefore, the interaction parmeters

for all pairs of atoms have to be read in.

These files are named like oo.spl, on.spl, oc.spl, no.spl etc.,

where oo.spl contains the two-center integrals for the O-O interaction,

on.spl the two-center integrals for the O-N interaction etc.

DFTB needs these parameters for the O-N and N-O interaction,

similarily for all other pairwise interactions.

The file sccdftb.dat contains the paths to these parameters, as:

'potential:atom-1-atom-1'

'potential:atom-1-atom-2'

'potential:atom-1-atom-3'

... \\

'potential:atom-1-atom-N'

'potential:atom-2-atom-1'

... \\

'potential:atom-2-atom-N'

'potential:atom-N-atom-1'

... \\

'potential:atom-N-atom-N'

where atom-1 is the atom defined by 1.0, as described above,

atom-2 defined in WMAIN by 2.0 etc.

If open-shell treatment via UNPE is specified, SCC-DFTB needs to read

in the spin-polarization constants. These are listed directly after the

parameter files section, one line for each atom type as defined in

WMAIN and following the same order as above (first line for atom-1,

second line for atom-2, and so on). Each line needs to look like:

spin-'dummy' Wss Wsp Wps Wpp Wsd Wpd Wdd Wds Wdp

where for readability 'dummy' can be the name of the atom type (e.g. c

for carbon). Values for the constants Wss,... can be found in the

Dissertation thesis of Christof Koehler, 2003, Unviversity Paderborn,

page 114f, which is also available online via

http://digital.ub.uni-paderborn.de/hs/content/titleinfo/3163

When third order DFTB is invoked via D3RD (or the now obsolete keyword

DHUB) the Hubbard derivatives Ud need to be specified following the

parameter file section, or the spin-section if the UNPE keyword is used:

'dummy' Ud-atom1

'dummy' Ud-atom2

...

For values of Ud see JCTC 2011,7,931.

When D3RD and LDEP is specified the Hubbard derivatives section looks

like:

'dummy' Ud-atom1-d-orbital Ud-atom1-p-orbital Ud-atom1-s-orbital

'dummy' Ud-atom2-d-orbital Ud-atom2-p-orbital Ud-atom2-s-orbital

...

If DHGA is specified (again, this is an obsolete option and was only

used in combination with DHUB), one line containing three number follow

in the form:

v0_hgau alp_hgau q0_hgau

For details see JCTC 2008,4,2067.

For HBON one additional parameter 'zeta' is necessary which is set as a

single number in a single line following all previous sections (if

invoked via corresponding keyword).

An example of a system containing O N C and H and having specified the

keywords UNPE 1.0, D3RD, and HBON, sccdftb.dat would look like:

'PATH/oo.spl'

'PATH/on.spl'

'PATH/oc.spl'

'PATH/oh.spl'

'PATH/no.spl'

'PATH/nn.spl'

'PATH/nc.spl'

'PATH/nh.spl'

'PATH/co.spl'

'PATH/cn.spl'

'PATH/cc.spl'

'PATH/ch.spl'

'PATH/ho.spl'

'PATH/hn.spl'

'PATH/hc.spl'

'PATH/hh.spl'

spin-o -0.035 -0.030 -0.030 -0.028 0.0 0.0 0.0 0.0 0.0

spin-n -0.033 -0.027 -0.027 -0.026 0.0 0.0 0.0 0.0 0.0

spin-c -0.031 -0.025 -0.025 -0.023 0.0 0.0 0.0 0.0 0.0

spin-h -0.072 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0

'o' -0.19

'n' -0.13

'c' -0.23

'h' -0.16

4.2

where PATH specifies the path to the directory where the data files

are located. Be careful, an error in the sequence or a wrong assingnment

of parameters to atoms (coordinates) will make results meaningless.

Parameter files can be downloaded at www.dftb.org or

requested from Marcus Elstner (marcus.elstner@kit.edu).

Another input file is necessary if the CDKO keyword is applied.

It contains two parameters for each QM atom type and one atom-size

describing parameter for each element appearing in the MM part. The

file is called ko_para.inp and needs to look like:

nQMatomtypes nMMelements

WMAIN:atom-1 a:atom-1 b:atom-1

WMAIN:atom-2 a:atom-2 b:atom-2

... ...

WMAIN:nQMatomtypes a:atom-nQMatomtypes b:atom-nQMatomtypes

<blank line>

name:MMelement1 U:MMelement1

name:MMelement2 U:MMelement2

... ...

name:nMMelements U:nMMelements

For the sccdftb.dat example above, the number of QM atomtypes is

nQMatomtypes = 4 (O,N,C, and H), if the MM part is composed solely out

of water the number of MM elements nMMelements = 2, where

name:MMelement1 is O and name:MMelement2 is H. a, b, and U are the

corresponding parameters published for phosphate

hydrolysis reactions (Hou, Cui, 8, 4293-4304 (2012)).

An example for this scheme is provided in test/c37test/sccdftb_cdko.inp

For additional discussion on the CDKO parameters, see, JPC, B 118, 11007-11027 (2014).

SCCDFTB output files (currently disabled)

-----------------------------------------

SPE.DAT : contains the Kohn-Sham energies with occupations numbers.

CHR.DAT : contains the atomic (Mulliken) charges of the atoms

(first row) and for the orbitals (s, px,py,pz,dxx.. ) in the

following columns.

REST.DAT: contains dipolemoment (D), calculated from the Mulliken

charges (not a reliable estimate of Dipolemoment in general!)

Top

Installation of SCCDFTB

-----------------------

The source code of SCCDFTB ist distributed with CHARMM.

To compile the SCCDFTB method as the quantum part:

./install machine size T

T invokes the SCCDFTB

The parameter files have to be reqeusted and stored in a directory,

which can be reached by 'PATH' (see up).

To enable the DFTB+ interface, three steps must be taken:

1) Obtain and compile the DFTB+ library - instructions

must be found elsewhere.

2) Modify the Makefile_${em64t|gnu} for proper linking, etc.:

2a) Add the directory where libdftb+ is compiled to the $INCLUDE

environment variable in the makefile:

LIBDFTBDIR = /path/to/dftbplus_source/api/charmm/_obj_x86_64-linux-ifort

INCLUDE = -I$(LIBDFTBDIR)

2b) Modify the link-line to properly link to libdftb+, e.g. for Makefile_em64t

$(LD) -o charmm.exe $(LIB)/*.o $(LIBDFTBDIR)/_dir_extlib_xmlf90/*.o $(LIBDFTBDIR)/*.o \

$(LIBS) $(LIBS) $(LIBS) $(ADDLIB) $(QLIB) $(MSGLIB) -I$(LIBDFTBDIR)/ \

-I$(LIBDFTBDIR)/_dir_extlib_xmlf90 $(MATHLIBS)

where $(MATHLIBS) is the link options to BLAS/LAPACK (usually MKL).

3) use the "+DFTBPLUS keyword" to compile, e.g.:

./install machine size T +DFTBPLUS

4) Use the PLUS keyword in the SCCDFTB group to run using the DFTB+ engine.

Installation of SCCDFTB

-----------------------

The source code of SCCDFTB ist distributed with CHARMM.

To compile the SCCDFTB method as the quantum part:

./install machine size T

T invokes the SCCDFTB

The parameter files have to be reqeusted and stored in a directory,

which can be reached by 'PATH' (see up).

To enable the DFTB+ interface, three steps must be taken:

1) Obtain and compile the DFTB+ library - instructions

must be found elsewhere.

2) Modify the Makefile_${em64t|gnu} for proper linking, etc.:

2a) Add the directory where libdftb+ is compiled to the $INCLUDE

environment variable in the makefile:

LIBDFTBDIR = /path/to/dftbplus_source/api/charmm/_obj_x86_64-linux-ifort

INCLUDE = -I$(LIBDFTBDIR)

2b) Modify the link-line to properly link to libdftb+, e.g. for Makefile_em64t

$(LD) -o charmm.exe $(LIB)/*.o $(LIBDFTBDIR)/_dir_extlib_xmlf90/*.o $(LIBDFTBDIR)/*.o \

$(LIBS) $(LIBS) $(LIBS) $(ADDLIB) $(QLIB) $(MSGLIB) -I$(LIBDFTBDIR)/ \

-I$(LIBDFTBDIR)/_dir_extlib_xmlf90 $(MATHLIBS)

where $(MATHLIBS) is the link options to BLAS/LAPACK (usually MKL).

3) use the "+DFTBPLUS keyword" to compile, e.g.:

./install machine size T +DFTBPLUS

4) Use the PLUS keyword in the SCCDFTB group to run using the DFTB+ engine.

Top

Free energy perturbations with SCC-DFTB/MM

The code currently allows dual-topology based SCC-DFTB/MM free energy

perturbation calculations; since all scaling related to the QM component

of the free energy derivative is done inside SCC-DFTB, the FEP

calculations do not have to use BLOCK.

As discussed in JPC, 107, 8643 (2003), a practical problem of using

FEP with QM/MM potentials is that the structure of the QM region

undergoes significant distortions at end-points if one scales the entire

QM molecule; there is no such problem if one chooses to scale only

QM/MM interactions, but that requires calculation of new terms. The

general solution is to add harmonic constraints on the QM part -

either only at the end-points and then re-weight the calculated free

energy derivatives - or, more elegantly, add harmonic constraints

as "chaperones" throughout the "alchemy" simulation and compute

corrections based on local configuration integrals. See W. Yang et al.

J. Chem. Phys. 2004.

For the special case where the two end-states have very similar chemical

structures - such as in redox, metal-exchange and pKa applications,

which we believe are scenarios where QM/MM treatment is useful, a simple

dual-topology-single-coordinate (DTSC) approach has been introduced. As

the name implies, one uses only one set of coordinates for the two

states (e.g., reduced and oxidized states). Due to the fact that the

free energy is path-independent, such an approach is formally exact. In

practical applications, error might arise due to SHAKE - i.e. X-H

distances are assumed to the same in the two states - which usually has

negligible effects.

At each configuration (hence single-coordinate) along the trajectory,

two electronic structure calculations are carried out (dual topology)

and the free energy derivative with respect to the coupling parameter

is evaluated and averaged on the fly.

With minor modifications, the algorithm also works for pKa prediction

for a specific group in large molecules. For more details, refer to the

following publications:

M. Formaneck, G. Li, X. Zhang, Q. Cui, J. Thero. Comput. Chem.

1, 53-68 (2002)

G. Li, X. Zhang, Q. Cui, J. Phys. Chem. B (2003) 107, 8643

G. Li, Q. Cui, J. Phys. Chem. B, (2003) 107, 14521

NOTE BENE: It MUST be used with "FAST OFF" because only generic

atom-atom codes have been modified so far (made default).

Due to the fact that ALL QM related components are handled within SCC

(including GSBP and eWald, see next section), FEP (such as pKa)

calculations can be used with both eWald and GSBP - provided that it is

the QM part that undergoes "alchemical" mutation.

The code has NOT been extensively tested in which both QM and MM

undergo changes.

Two examples are given to illustrate computational details; the

first one deals with redox potential calculations for FAD in Cholesterol

oxidase, and the second one concerns pKa calculations of ethanethiol

(Ch3CH2SH) in water. The test files are scc_fep_dtsc.inp and

scc_pka1/2.inp.

Example(1)

----------

For redox potential calculations, the following set-up is used,

......

SCCDFTB LAMDa [REST] STOP [CUTF] OUTPut int -

[REMOve] (atom selection 1) [CHRG] [TEMPerature] [SCFtolerance] -

[UNPE] -

INIT @lam PASS int STEP int TIAV int -

[CHRG] [TEMPerature] [SCFtolerance] -

[UNPE] -

(atom selection 2) -

(atom selection 3)

LAMD: invoke the TI method to perform free energy calculations

REST: Restart option for accumulating statistics concerning <DU/DL>

i.e., necessary values will be read in from dynamics restart

file

STOP: employ the dual-topology-single-coordinate approach

CUTF: invoke cutoff for QM/MM electrostatic interactions

OUTP: unit number for storing the free energy derivative <DU/DL>

INIT: the current lamda value

PASS: numbers of MD steps to be skipped when accumulating <DU/DL>

STEP: the frequency of collecting statistics for <DU/DL>

TIAV: the frequency of computing the average of DU/DL.

atom selection 1: Reactant+Product to set up MM list for QM atoms

atom selection 2: Reactant state

atom selection 3: Product state

--------------------------------------------------------------------

For pKa calculations, two free energy simulations are in

principle required; in the first step, the protonated state is mutated

into the ionized state as the acidic proton is mutated into a dummy atom

in the second step, the dummy atom is transferred into the gas phase.

Test calculations indicate that the contribution from the 2nd step is

likely to be small.

Example(2a)

----------

In the first step, BLOCK is used together with SCCDFTB

......

BLOCK 3

SCCDFTB STOP PKAC ISTP 1

CALL 2 SELE qm1 END

CALL 3 SELE qmh END

CALL 1 SELE .not. (qm1 .or. qmh) END

COEF 1 1 1.0

COEF 1 2 1.0

COEF 1 3 1.0

COEF 2 2 0.0

COEF 2 3 @lam

COEF 3 3 0.0

END

SCCDFTB PKAC ISTP 1 HYGN int [CUTF] OUTPut int -

[REMOve] (atom selection 1) [CHRG] [TEMPerature] [SCFtolerance] -

[UNPE] -

INIT @lam PASS int STEP int TIAV int -

[CHRG] [TEMPerature] [SCFtolerance] -

[UNPE] -

atom selection 2 -

atom selection 3

......

In the BLOCK section :

the SCCD keyword is used to set up coefficent matrix for calculating

bonded contribution involving the dummy atom to <DU/DL>.

ISTP 1: the first step in pKa calculations

qm1 is the ionized state (e.g., CH3CH2S-);

qmh is the acidic proton.

In the SCCDFTB section:

PKAC : invoke pKa calculation

ISTP 1: the first step in pKa calculations

HYGN : atomic index (number) of the acidic proton in the psf

atom selection 1: protonated state (CHRG: protonated state)

atom selection 2: protonated state (CHRG: deprotonated state)

atom selection 3: deprotonated state

Example(2b)

----------

In the second step for pKa calculations, the dummy atom is transferred

into vacuum,

......

calc 1mlam 1.0-@lam

BLOCK 3

SCCDFTB STOP PKAC ISTP 2

CALL 2 SELE qm1 END

CALL 3 SELE qmh END

CALL 1 SELE .not. (qm1 .or. qmh) END

COEF 1 1 1.0

COEF 1 2 1.0

COEF 1 3 @1mlam

COEF 2 2 0.0

COEF 2 3 0.0 bond 1.0 angl 1.0 dihe 1.0

COEF 3 3 0.0

END

SCCDFTB PKAC ISTP 2 HYGN int [CUTF] OUTPut int -

[REMOve] [CHRG] (atom selection 1) [TEMPerature] [SCFtolerance] -

INIT @lam PASS int STEP int TIAV int

......

Note that with BLOCK, the coefficient matrix is different in the

second step: we are only scaling the non-bond (vdW) interaction between

the environment and the dummy atom (1 and 3). The bonded terms between

the QM and the dummy atom (2 and 3) is kept (coefficient as 1.0) and

will be taken out with local configuration integrals.

In SCC-DFTB, atom selection 1: deprotonated state

Free energy perturbations with SCC-DFTB/MM

The code currently allows dual-topology based SCC-DFTB/MM free energy

perturbation calculations; since all scaling related to the QM component

of the free energy derivative is done inside SCC-DFTB, the FEP

calculations do not have to use BLOCK.

As discussed in JPC, 107, 8643 (2003), a practical problem of using

FEP with QM/MM potentials is that the structure of the QM region

undergoes significant distortions at end-points if one scales the entire

QM molecule; there is no such problem if one chooses to scale only

QM/MM interactions, but that requires calculation of new terms. The

general solution is to add harmonic constraints on the QM part -

either only at the end-points and then re-weight the calculated free

energy derivatives - or, more elegantly, add harmonic constraints

as "chaperones" throughout the "alchemy" simulation and compute

corrections based on local configuration integrals. See W. Yang et al.

J. Chem. Phys. 2004.

For the special case where the two end-states have very similar chemical

structures - such as in redox, metal-exchange and pKa applications,

which we believe are scenarios where QM/MM treatment is useful, a simple

dual-topology-single-coordinate (DTSC) approach has been introduced. As

the name implies, one uses only one set of coordinates for the two

states (e.g., reduced and oxidized states). Due to the fact that the

free energy is path-independent, such an approach is formally exact. In

practical applications, error might arise due to SHAKE - i.e. X-H

distances are assumed to the same in the two states - which usually has

negligible effects.

At each configuration (hence single-coordinate) along the trajectory,

two electronic structure calculations are carried out (dual topology)

and the free energy derivative with respect to the coupling parameter

is evaluated and averaged on the fly.

With minor modifications, the algorithm also works for pKa prediction

for a specific group in large molecules. For more details, refer to the

following publications:

M. Formaneck, G. Li, X. Zhang, Q. Cui, J. Thero. Comput. Chem.

1, 53-68 (2002)

G. Li, X. Zhang, Q. Cui, J. Phys. Chem. B (2003) 107, 8643

G. Li, Q. Cui, J. Phys. Chem. B, (2003) 107, 14521

NOTE BENE: It MUST be used with "FAST OFF" because only generic

atom-atom codes have been modified so far (made default).

Due to the fact that ALL QM related components are handled within SCC

(including GSBP and eWald, see next section), FEP (such as pKa)

calculations can be used with both eWald and GSBP - provided that it is

the QM part that undergoes "alchemical" mutation.

The code has NOT been extensively tested in which both QM and MM

undergo changes.

Two examples are given to illustrate computational details; the

first one deals with redox potential calculations for FAD in Cholesterol

oxidase, and the second one concerns pKa calculations of ethanethiol

(Ch3CH2SH) in water. The test files are scc_fep_dtsc.inp and

scc_pka1/2.inp.

Example(1)

----------

For redox potential calculations, the following set-up is used,

......

SCCDFTB LAMDa [REST] STOP [CUTF] OUTPut int -

[REMOve] (atom selection 1) [CHRG] [TEMPerature] [SCFtolerance] -

[UNPE] -

INIT @lam PASS int STEP int TIAV int -

[CHRG] [TEMPerature] [SCFtolerance] -

[UNPE] -

(atom selection 2) -

(atom selection 3)

LAMD: invoke the TI method to perform free energy calculations

REST: Restart option for accumulating statistics concerning <DU/DL>

i.e., necessary values will be read in from dynamics restart

file

STOP: employ the dual-topology-single-coordinate approach

CUTF: invoke cutoff for QM/MM electrostatic interactions

OUTP: unit number for storing the free energy derivative <DU/DL>

INIT: the current lamda value

PASS: numbers of MD steps to be skipped when accumulating <DU/DL>

STEP: the frequency of collecting statistics for <DU/DL>

TIAV: the frequency of computing the average of DU/DL.

atom selection 1: Reactant+Product to set up MM list for QM atoms

atom selection 2: Reactant state

atom selection 3: Product state

--------------------------------------------------------------------

For pKa calculations, two free energy simulations are in

principle required; in the first step, the protonated state is mutated

into the ionized state as the acidic proton is mutated into a dummy atom

in the second step, the dummy atom is transferred into the gas phase.

Test calculations indicate that the contribution from the 2nd step is

likely to be small.

Example(2a)

----------

In the first step, BLOCK is used together with SCCDFTB

......

BLOCK 3

SCCDFTB STOP PKAC ISTP 1

CALL 2 SELE qm1 END

CALL 3 SELE qmh END

CALL 1 SELE .not. (qm1 .or. qmh) END

COEF 1 1 1.0

COEF 1 2 1.0

COEF 1 3 1.0

COEF 2 2 0.0

COEF 2 3 @lam

COEF 3 3 0.0

END

SCCDFTB PKAC ISTP 1 HYGN int [CUTF] OUTPut int -

[REMOve] (atom selection 1) [CHRG] [TEMPerature] [SCFtolerance] -

[UNPE] -

INIT @lam PASS int STEP int TIAV int -

[CHRG] [TEMPerature] [SCFtolerance] -

[UNPE] -

atom selection 2 -

atom selection 3

......

In the BLOCK section :

the SCCD keyword is used to set up coefficent matrix for calculating

bonded contribution involving the dummy atom to <DU/DL>.

ISTP 1: the first step in pKa calculations

qm1 is the ionized state (e.g., CH3CH2S-);

qmh is the acidic proton.

In the SCCDFTB section:

PKAC : invoke pKa calculation

ISTP 1: the first step in pKa calculations

HYGN : atomic index (number) of the acidic proton in the psf

atom selection 1: protonated state (CHRG: protonated state)

atom selection 2: protonated state (CHRG: deprotonated state)

atom selection 3: deprotonated state

Example(2b)

----------

In the second step for pKa calculations, the dummy atom is transferred

into vacuum,

......

calc 1mlam 1.0-@lam

BLOCK 3

SCCDFTB STOP PKAC ISTP 2

CALL 2 SELE qm1 END

CALL 3 SELE qmh END

CALL 1 SELE .not. (qm1 .or. qmh) END

COEF 1 1 1.0

COEF 1 2 1.0

COEF 1 3 @1mlam

COEF 2 2 0.0

COEF 2 3 0.0 bond 1.0 angl 1.0 dihe 1.0

COEF 3 3 0.0

END

SCCDFTB PKAC ISTP 2 HYGN int [CUTF] OUTPut int -

[REMOve] [CHRG] (atom selection 1) [TEMPerature] [SCFtolerance] -

INIT @lam PASS int STEP int TIAV int

......

Note that with BLOCK, the coefficient matrix is different in the

second step: we are only scaling the non-bond (vdW) interaction between

the environment and the dummy atom (1 and 3). The bonded terms between

the QM and the dummy atom (2 and 3) is kept (coefficient as 1.0) and

will be taken out with local configuration integrals.

In SCC-DFTB, atom selection 1: deprotonated state

Top

Since 2004, electrostatics in SCC-DFTB/MM simulations can be

treated in several ways for both spherical and periodic conditions:

i). As for other QM packages, the default is no cut-off for QM/MM

electrostatic interactions. This is NOT recommended when cut-off

is used for MM; the imbalance will cause over-polarization of the media

(e.g.,see discussion in classical simulations by Woods, J. Chem. Phys.

103, 6177, 1995). A useful option is to use extended electrostatics for

MM.

ii). Cut-off is introduced for QM/MM electrostatics, similar to MM

interactions; i.e., the same scaling factors are the same as those for

MM interactions. Simply add "CUTF" to the SCC-DFTB command line.

Currently only supports energy/force-shifts based on atoms

iii). For spherical boundary conditions, the

GSBP approach can now be used with SCC-DFTB. The current implementation

takes GSBP contributions into the SCF iteration, although for a large

inner region, this may not be necessary. Further tests are being carried

out. The code will be extended to other boundary conditions and QM

methods in the future. If one uses sorting (i.e., truncate size of

basis in GSBP), make sure a SCC-DFTB/MM

energy calculation with MULL (save Mulliken charge) is carried out

before issuing GSBP, since the Mulliken charges are used to estimate

contributions from various basis functions to the QM related terms.

See test cases for examples.

The GSBP and PB reference calculations are made consistent in terms of

reference state and the boundaries are updated in the PB calculations.

Simple test on a simple sodium ion led to correct answer with different EPSP

values.

The implementation is described in: J. Chem. Phys. 123, 014905 (2005).

iv). For PBC simulations, one can use either cut-off or eWald sum for

SCC-DFTB/MM interactions. Also PME has been implemented for the QM/MM

interactions but no extensive performance checks have been carried out

yet. The current QM/MM implementation allows in principle all cell shapes.

For eWald, one can either let the code optimize the exponent to get the

best balance between real space sum and the reciprocal space sum (EOPT)

or one can specify a set of parameters (Kappa, KMAX, KSQMAX).

The real space sum is done till convergence is met with EOPT or

without CUTF (so more expensive); EOPT is incompatible with CUTF.

With cutoff (CUTF), the real sum is limited to atoms within the cutoff-

which is recommended (much more efficient). In any case, one should

carefully test kappa, KMAX to ensure the convergence of energy and,

more importantly, force from SCC-DFTB/MM calculations.

A sample command line would be:

......

SCCDFTB remove CHRG 2 SELE resn @m END TEMP 0.00 SCFT 0.00000001 EWAD -

CUTF Kappa 0.45 KMAX 6 KSQMAX 100

......

With the 2009 implementation, QM/MM-eWald without CUTF is about 4-6

times slower than a QM/MM calculation without eWald (i.e., with only cutoff).

With real-space cutoff (CUTF), QM/MM-eWald is only slightly slower than QM/MM

without eWald. In 2012, QM/MM-PME has been implemented for SCC-DFTB by the

Gao group. For an example, see test/c37test/sccdftb_pme.inp.

The eWald implementation is described in: J. Phys. Chem. B 109, 17715-17733

(2005). The PME implementation follows the same approach as established for

SQUANTM as described in J. Chem. Theory Comput, 1, 2-13 (2005).

An important point for PBC simulations is that all image must be used

with "UPDAte IMAL ". This is because symmetry operations have not been

considered in the SCC-DFTB/MM code - which obviously needs to be fixed

in the future.

The eWald implementation is described in: J. Phys. Chem. B 109, 17715-17733

(2005)

v). SCC-DFTB has been implemented to work with Poisson-Boltzmann, which

allows to calculate solvation free energy and optimize reaction path with

implicit solvent. Several keywords are added to the PBEQ module:

PSTL(0.01 kcal/mol): Energy convergence criterion of the iterative

QM-PB calculation

MXPS(5000): Maximum # of SCC and PB solver iterations.

IGAS: flag to initiate calculation from gas phase in every step,

otherwise from last step (this is default for solvation free

energy calculation).

CHDR: instead of a fixed set of atomic radii, use charge-depdent radii,

which can be useful for charged species (Hou, Zhu and QC,

unpublished). In this case, a file named radius.inp, which

contains optimized parameters for the charge-dependence of atomic

radius, must be included in the local directory, similar to

sccdftb.dat.

For details please refer test cases: test_sccpb.inp

Since 2004, electrostatics in SCC-DFTB/MM simulations can be

treated in several ways for both spherical and periodic conditions:

i). As for other QM packages, the default is no cut-off for QM/MM

electrostatic interactions. This is NOT recommended when cut-off

is used for MM; the imbalance will cause over-polarization of the media

(e.g.,see discussion in classical simulations by Woods, J. Chem. Phys.

103, 6177, 1995). A useful option is to use extended electrostatics for

MM.

ii). Cut-off is introduced for QM/MM electrostatics, similar to MM

interactions; i.e., the same scaling factors are the same as those for

MM interactions. Simply add "CUTF" to the SCC-DFTB command line.

Currently only supports energy/force-shifts based on atoms

iii). For spherical boundary conditions, the

GSBP approach can now be used with SCC-DFTB. The current implementation

takes GSBP contributions into the SCF iteration, although for a large

inner region, this may not be necessary. Further tests are being carried

out. The code will be extended to other boundary conditions and QM

methods in the future. If one uses sorting (i.e., truncate size of

basis in GSBP), make sure a SCC-DFTB/MM

energy calculation with MULL (save Mulliken charge) is carried out

before issuing GSBP, since the Mulliken charges are used to estimate

contributions from various basis functions to the QM related terms.

See test cases for examples.

The GSBP and PB reference calculations are made consistent in terms of

reference state and the boundaries are updated in the PB calculations.

Simple test on a simple sodium ion led to correct answer with different EPSP

values.

The implementation is described in: J. Chem. Phys. 123, 014905 (2005).

iv). For PBC simulations, one can use either cut-off or eWald sum for

SCC-DFTB/MM interactions. Also PME has been implemented for the QM/MM

interactions but no extensive performance checks have been carried out

yet. The current QM/MM implementation allows in principle all cell shapes.

For eWald, one can either let the code optimize the exponent to get the

best balance between real space sum and the reciprocal space sum (EOPT)

or one can specify a set of parameters (Kappa, KMAX, KSQMAX).

The real space sum is done till convergence is met with EOPT or

without CUTF (so more expensive); EOPT is incompatible with CUTF.

With cutoff (CUTF), the real sum is limited to atoms within the cutoff-

which is recommended (much more efficient). In any case, one should

carefully test kappa, KMAX to ensure the convergence of energy and,

more importantly, force from SCC-DFTB/MM calculations.

A sample command line would be:

......

SCCDFTB remove CHRG 2 SELE resn @m END TEMP 0.00 SCFT 0.00000001 EWAD -

CUTF Kappa 0.45 KMAX 6 KSQMAX 100

......

With the 2009 implementation, QM/MM-eWald without CUTF is about 4-6

times slower than a QM/MM calculation without eWald (i.e., with only cutoff).

With real-space cutoff (CUTF), QM/MM-eWald is only slightly slower than QM/MM

without eWald. In 2012, QM/MM-PME has been implemented for SCC-DFTB by the

Gao group. For an example, see test/c37test/sccdftb_pme.inp.

The eWald implementation is described in: J. Phys. Chem. B 109, 17715-17733

(2005). The PME implementation follows the same approach as established for

SQUANTM as described in J. Chem. Theory Comput, 1, 2-13 (2005).

An important point for PBC simulations is that all image must be used

with "UPDAte IMAL ". This is because symmetry operations have not been

considered in the SCC-DFTB/MM code - which obviously needs to be fixed

in the future.

The eWald implementation is described in: J. Phys. Chem. B 109, 17715-17733

(2005)

v). SCC-DFTB has been implemented to work with Poisson-Boltzmann, which

allows to calculate solvation free energy and optimize reaction path with

implicit solvent. Several keywords are added to the PBEQ module:

PSTL(0.01 kcal/mol): Energy convergence criterion of the iterative

QM-PB calculation

MXPS(5000): Maximum # of SCC and PB solver iterations.

IGAS: flag to initiate calculation from gas phase in every step,

otherwise from last step (this is default for solvation free

energy calculation).

CHDR: instead of a fixed set of atomic radii, use charge-depdent radii,

which can be useful for charged species (Hou, Zhu and QC,

unpublished). In this case, a file named radius.inp, which

contains optimized parameters for the charge-dependence of atomic

radius, must be included in the local directory, similar to

sccdftb.dat.

For details please refer test cases: test_sccpb.inp

Top

Description of the GLNK Command

[GLNK atom-selection]

atom-selection: contains a list of atoms that are boundary atoms.

Restrictions: see the correponding entry for GLNK in quantum.info

Description: see the correponding entry for GLNK in quantum.info

Limitations: The present implementation allows up to 5 QM-boundary

atoms. To improve the geometry for the QM/MM boundary bond, an

empirical correction (Ecor) term is added. Currently, Ecor parameters

are only available for cases where the QM/MM partition cuts a C-C,

a C-O, or a C-S bond. For other cases, no empirical corrections

will be included. Unrestricted GHO-SCC-DFTB for open-shell system

is not implemented.

Reference: Reference made to the following paper, which contains

a more thorough description and discussion of test cases, is appreciated.

Jingzhi Pu, Jiali Gao, and Donald G. Truhlar,

J. Phys. Chem. A 108, 5454-5463 (1998). "Combining Self-Consistent-Charge

Density-Functional Tight-Binding (SCC-DFTB) with Molecular Mechanics by

the Generalized Hybrid Orbital (GHO) Method."

Description of the GLNK Command

[GLNK atom-selection]

atom-selection: contains a list of atoms that are boundary atoms.

Restrictions: see the correponding entry for GLNK in quantum.info

Description: see the correponding entry for GLNK in quantum.info

Limitations: The present implementation allows up to 5 QM-boundary

atoms. To improve the geometry for the QM/MM boundary bond, an

empirical correction (Ecor) term is added. Currently, Ecor parameters

are only available for cases where the QM/MM partition cuts a C-C,

a C-O, or a C-S bond. For other cases, no empirical corrections

will be included. Unrestricted GHO-SCC-DFTB for open-shell system

is not implemented.

Reference: Reference made to the following paper, which contains

a more thorough description and discussion of test cases, is appreciated.

Jingzhi Pu, Jiali Gao, and Donald G. Truhlar,

J. Phys. Chem. A 108, 5454-5463 (1998). "Combining Self-Consistent-Charge

Density-Functional Tight-Binding (SCC-DFTB) with Molecular Mechanics by

the Generalized Hybrid Orbital (GHO) Method."

Top

The current implementation has analytical first derivative and thus

allows energy minimizations, reaction path search (e.g., travel) and

molecular dynamics simulations; SCC-DFTB/MM also works with Monte Carlo.

Replica can also be used, which makes it possible to use replica path

and related approaches (such the nudged elastic band) for determining

reaction path with the SCC-DFTB/MM potential; along the same line,

path integral simulations can be carried out as well, although only for

equilibrium properties at this stage.

Several aspects of the code will be improved in the near future,

and new functionalities will be added:

1. Interface with centroid path-integral simulations and Tsallis

statistics.

2. More flexible interface with BLOCK for general free energy

simulations.

3. Better methods for open-shell systems; constrained density functional

theories.

4. Time-dependent treatment for electronically excited states; non-adiabtic MD.

5. Integration with polarizable force field models (Drude).

The current implementation has analytical first derivative and thus

allows energy minimizations, reaction path search (e.g., travel) and

molecular dynamics simulations; SCC-DFTB/MM also works with Monte Carlo.

Replica can also be used, which makes it possible to use replica path

and related approaches (such the nudged elastic band) for determining

reaction path with the SCC-DFTB/MM potential; along the same line,

path integral simulations can be carried out as well, although only for

equilibrium properties at this stage.

Several aspects of the code will be improved in the near future,

and new functionalities will be added:

1. Interface with centroid path-integral simulations and Tsallis

statistics.

2. More flexible interface with BLOCK for general free energy

simulations.

3. Better methods for open-shell systems; constrained density functional

theories.

4. Time-dependent treatment for electronically excited states; non-adiabtic MD.

5. Integration with polarizable force field models (Drude).