VisualForceFieldDerivationToolkit(VFFDT)

Manual
1. Brief introduction to VFFDT ..................................................................................................................1
2. Installation Notes for VFFDT .................................................................................................................1
2.1 System requirement for VFFDT .....................................................................................................1
2.2 Download site for VFFDT ..............................................................................................................1
3. Brief introduction to the method used in VFFDT ...................................................................................2
4. Tutorials for VFFDT ...............................................................................................................................4
4.1 Derivation of force field parameter based on QM computation .......................................................4
4.2 Force field derivation on-the-fly with Semi-empirical based hessian matrix .................................15
4.3 Various VFFDT utilities complementary to the AmberTools .........................................................21
5. Contact Information ..............................................................................................................................38
6. Reference ..............................................................................................................................................39
 VFFDT Manual 1

1. Brief introduction to VFFDT

Visual Force Field Derivation Toolkit (VFFDT) was developed to derive bond stretching
and bond angle bending force field parameters for metal-containing molecular systems based
on the Seminario method. The main interface of VFFDT is displayed in Figure 1. The basic
functions of this software include: (1) 3D operation on a molecular structure, such as translation,
rotation, and scaling; (2) Rendering a molecule in different styles, such as the ball-and-stick
model and the space-filling model; (3) Reading the outputs of Quantum Mechanics package
such as Gaussian03/09, QChem, MOPAC2009/2012, Gamess, and ORAC3.0; (4) Outputting
molecular structures in the SYBYL Mol2 format, the RCSB PDB format, the standard XYZ
format, and the VFFDT XYZ format; (5) Setting up parameters for a Gaussian job; (6) The
parameterization module for a metal-containing system. After well testing, currently this tool
can be run in the Windows Operating Systems such as XP, Win7, Win8, and Win10, and can
be obtained freely upon request from either of the following three ways:
(1) Directly from the author Lin Fu via email
lin1449@126.com
(2) Baidu Cloud Disk
http://pan.baidu.com/share/home?uk=2642812499
(3) Dropbox shared folder
https://www.dropbox.com/sh/hlefz8xy8o23q44/AADZGTBN-aJ07flZ-kM0s4U6a?dl=0

2. Installation Notes for VFFDT

2.1 System requirement for VFFDT

VFFDT program can be run on the following operating systems:

Microsoft Windows XP, WIN7, WIN8, and WIN10

2.2 Download site for VFFDT

Latest version of VFFDT installation package can be requested from author Lin Fu via
email (lin1449@126.com) or from the websites mentioned above. There are two binary
versions based on different OSs.
 VFFDT Manual 2

OS Installation Package
Microsoft Windows 32bit VFFDT_version1_belta_Setup_32bit.exe
Microsoft Windows 64bit VFFDT_version1_belta_Setup_64bit.exe

3. Brief introduction to the method used in VFFDT

(1 cosn )
Vn
K K (
2 2
U ( R) r ( r req ) eq )
bonds angles dihedrals 2
atoms Aij Bij atoms qi q j (1)
(R
i j
12

Rij6
)
i j Rij
ij

Where K r , req , K , eq ,Vn , n, , Aij , Bij , are the parameters for this AMBER form of

potential energy function. The Force field parameter in Equation 1 can be deducted from this
hessian matrix. We briefly describe this method as follow. For a system of N atoms, the 3N
component reaction force due to a displacement of the N atoms in a molecular system can be
expressed by a Taylor expansion to the second order as follows.

F k x (2)
is the hessian matrix. The full form of Equation 2 is shown below and each element
in the matrix will be obtained from the QM calculations.

2E 2E 2E 2E

x12 x1x 2 x1x3 x1x3 N x
F1 E
2
2E 2E 2E 1
F x x
x 2
2 x 22 x 2 x3 x 2 x3 N
22 1
F3 E 2E 2E 2E x 3





x3 x1 x3 x 2 x32 x3 x3 N







F 2
x3 N

3N
E E
2
E
2
E
2

x x x3 N x 2 x3 N x3

x32N
3N 1 (3)

To calculate bond stretching force constant of bond AB, 33 matrix is extracted

from the hessian matrix above.

FA k AB xB (4)
 VFFDT Manual 3

2E 2E 2E

FAx x A2x B x A y B x A z B x
B
F E 2E 2E
y B
Ay y x y A x B y A x B
FAz A2 B z
E 2E 2E B
z A x B z A x B z A x B
(5)
The force in Equation 4 represents the response force in atom A due to a displacement in
atom B. Diagonalization of the 3 3 matrix yields the eigenvalues and
corresponding eigenvectors .
3
k AB iAB u AB iAB
i 1 (6)
While is the harmonic force constant for bond stretching; is distance vector
pointing from atom A to atom B.
Similarly, the angle bending force constant of angle ABC can also be calculated using
Equation 7-9.
2E 2E 2E

F Ax x A2x B x A y B x A z B x
B
F E 2E 2E
y B
Ay y x y A x B y A x B
F Az A2 B z
E 2E 2E B
z A x B z A x B z A x B
(7)
2E 2E 2E

FCx xC2x B xC y B xC z B x
B
F E 2E 2E
y B
Cy y x y C x B y C x B
FCz C2 B z
E 2E 2E B
z C x B z C x B z C x B
(8)
1 1 1
3
3
k
d AB2 iAB u PA iAB d CB2 CB
i u
PC
iCB
i 1 i 1 (9)

Here, dAB and dCB are the distances between atoms A-B and C-B, respectively; Where

; ; . , , , , ,

and
have similar meanings as in Equation 6.
 VFFDT Manual 4

4. Tutorials for VFFDT

The major features of VFFDT program(1) Derivation of force field parameter based on
QM (Especially metal-containing system); (2) Force field derivation on-the-fly with Semi-
empirical based hessian matrix; (3) Various VFFDT utilities complementary to the
AmberTools.

4.1 Derivation of force field parameter based on QM computation

Force field parameters missing problem is common in the practical MD simulation,

especially for the metal-containing system. In this tutorial, we take the [Zn(imidazole)4]2+ as
an example to derive the zinc related force field parameter such as bond stretching force
constant of Zn-N and angle bending force constant of N-Zn-N.
(1) Open the file Zn-his-his-his-his.mol2 (Figure 1) with the VFFDT program (Note: the file
Zn-his-his-his-his.mol2 is located in %installation-path%\test\tutorial_001\).

Figure 1. Main viewer window of VFFDT.

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(2) Click on the menu ProtocolGaussian QM Settings to open the window titled Gaussian
QM Settings (Figure 2), set up the Gaussian keyword #p freq=noraman b3lyp/6-
311++g(2d,2p) iop(7/33=1), and save the Gaussian input file as Zn-his-his-his-his-freq-6-
311++G-2d2p.gjf. If the Gaussian software has been installed in the machine, users can
directly click on the command Submit Job to Localhost, and the job management
window titled Submit Job To LocalHost (Figure 3) will pop out for users to submit and
manage multiple jobs with background mode. Once the job is finished, the Gaussian output
will be generated called Zn-his-his-his-his-freq-6-311++G-2d2p.out, which is located
in %installation-path%\test\tutorial_001\.

Figure 2. The window titled Gaussian QM Settings.

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Figure 3. The window titled Submit Job To LocalHost.

(3) Open the Gaussian output file Zn-his-his-his-his-freq-6-311++G-2d2p.out. If this output

file has been obtained in advance, Step (1) and (2) can be skipped.
(4) Click on the menu ProtocolFreq Scaling Factor (Figure 4), where users can set the
frequency scaling factor based on the basis set adopted in their own Gaussian
computation. In this tutorial this factor will be set at 0.978121 based on the Gaussian 03
manual.
 VFFDT Manual 7

Figure 4. Menu Protocol and Input box for the frequency scaling factor.

(5) Derive the force constant for the bond stretching. VFFDT offers three methods: (a) click

on the icon on the toolbar and select two atoms in the viewer (Figure 5), then the force

field parameter for this bond will be automatically shown in the window titled Console
Log, which can be open via clicking the menu WindowsShow Log; (b) The bond
stretching force constant can also be derived in the Console Log with the following
command >>pick 1 18 or >>pick 18 1 (1 and 18 are atom IDs for these two atoms in
specific bond, Figure 6); (c) Click on the menu ProtocolFF For the Metal Containing
Region OnlyZn Force Field, then all the bond stretching force constants related with
zinc will be derived by clicking on the command Generate All Parameters
Automatically in the window titled Zn Related Force Field Parameters, meanwhile
the AMBER atomic type will be assigned automatically via clicking on the command
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Assign AMBER GAFF Atom Type(Figure 7).

Figure 5. Derivation of bond related force field parameter via clicking on the atoms in the
viewer. Note: the bond force constant is an average value due to its asymmetric submatrix
 VFFDT Manual 9

for the specific bond.

Figure 6. Derivation of bond related force field parameter via the command line pick 1
18 in the console window.
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Figure 7. Derivation of Zinc related force field parameter (including both bond stretching
and angle bending force constant) via clicking on the menu ProtocolFF For the Metal
Containing Region OnlyZn Force Field. Note: (1) Users can manually customize the
Atomic type based on their definition; (2) The dihedral parameters will not be assigned
since the Seminario method cannot obtain the force constant for the dihedral term with
cosine function in AMBER.

(6) Derive the force constant for the angle bending. VFFDT also provides three methods: (a)

click on the icon on the toolbar and select three atoms in the viewer (Figure 8), then

angle bending force constant for this angle will be automatically printed in the window
titled Console Log, which can be open via clicking on the menu WindowsShow Log;
(b) The angle bending force constant can also be derived in the Console Log with the
command line>>pick 2 1 18 (2, 1 and 18 are atom IDs for these three atoms in specific
angle, Figure 9); (c) Click the menu Protocol FF For the Metal Containing Region
OnlyZn Force Field, and all the angle bending force constants related with zinc will
be derived by clicking on the command Generate All Parameters Automatically in the
window titled Zn Related Force Field Parameters, meanwhile the AMBER atomic
 VFFDT Manual 13

type will be assigned automatically via clicking on the command Assign AMBER GAFF
Atom Type (Figure 7).

Figure 8. Derivation of angle related force field parameter via clicking on the atoms in the
viewer.
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Figure 9. Derivation of angle related force field parameter via the command line pick 2 1
18 in the console window.
 VFFDT Manual 15

4.2 Force field derivation on-the-fly with Semi-empirical based hessian matrix

VFFDT has implemented the Instant FF derivation protocol to quickly derive the force
field with semi-empirical quantum mechanics (SQM) method. Here we take benzene molecule
as an example to derive its bond or angle related force field parameters. The whole procedure
will be described as follow.
(1) Load the MOL2 file benzene.mol2 into the viewer window (Figure 10). (Note: the
file benzene.mol2 is located in the %installation-path%\test\tutorial_002\).

Figure 10. Benzene molecule loaded in the viewer window.

(2) Click on the menu Protocol Instant FF Derivation (Figure 11), then a panel titled
Instant FF Derivation (Figure 12) pops out and waits for users to input the charge and
multiplicity of the molecule in the viewer window.


 VFFDT Manual 16

Figure 11. The Instant FF Derivation protocol in the menu Protocol.

Figure 12. Panel titled Instant FF Derivation.

(3) Click on the command Submit Job to Localhost and the window titled Submit Job to
Localhost (Figure 12) will show the state of the jobs.
 VFFDT Manual 17

Figure 13. The window titled Submit Job To LocalHost.

(4) Users can double-click on the cell with column header JobLogDirectory once the job is
finished, and the Gaussian output benenze.out will be automatically loaded into the main
viewer.
 VFFDT Manual 18

Figure 14. FF for the Whole General Small Molecule in the menu Protocol.

(5) Click on the Protocol FF for the Whole General Small Molecule in the menu
Protocol (Figure 14), then the panel titled All Related Force Field Parameters can
assign the AMBER GAFF atomic type automatically and derive all the parameters for the
bond and angle term for the benzene (Figure 15).
VFFDT Manual 19

 VFFDT Manual 20

Figure 16. Force Field Derivation for the small molecule using the window titled All
Related Force Field Parameters
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4.3 Various VFFDT utilities complementary to the AmberTools

VFFDT can read AMBER Prepc and Frcmod files from ANTECHAMBER in AmberTools.
Users can visualize the AMBER atomic type, modify the AMBER atomic type and write the
AMBER Prepc and Frcmod files. In the following part, we take phenol molecule as an instance
to customize the atomic type, add the missing parameters with Seminario method, and generate
the AMBER topology file with the help of both VFFDT and AmberTools.

(1) Load the Mol2 file phenol.mol2 into the VFFDT viewer window (Figure 17). (Note: the
file phenol.mol2 is located in %installation-path%\test\tutorial_003\).

Figure 17. Phenol molecule with Mol2 format is loaded in the viewer window. The atom
ID can be shown via clicking the menu ViewLabelAtom ID.

(2) The MOL2 file phenol.mol2 can be transformed into the AMBER prepc file
phenol.prepc and AMBER frcmod file phenol.frcmod in the ANTECHAMBER with
 VFFDT Manual 22

the commands in the Figure 18. (Note: the file phenol_resp.gjf, phenol_resp.out,
phenol_resp.prepc, and phenol_resp.frcmod have been saved in the %installation-
path%\test\tutorial_003\).

Figure 18. The commands used to generate AMBER prepc and frcmod files with complete
parameters via the ANTECHAMBER in the AmberTools. Note: in the parmchk command,
please use the flag -a Y to write all the related parameters in the AMBER frcmod file.

(3) Load the AMBER prepc file phenol_resp.prepc into the VFFDT viewer window (Figure
18). (Note: this file is located in %installation-path%\test\tutorial_003\).

VFFDT Manual 23

 VFFDT Manual 24

Figure 19. Phenol molecule with AMBER Prepc format is loaded in the VFFDT viewer
window. The atom ID, AMBER atomic type, AMBER chain symbol, and atomic partial
charge can be shown via clicking the menu ViewLabelAmber Type,
ViewLabelAmber Type, ViewLabelAmber Chain, and
ViewLabelAtom Charge respectively. Note: the atom ID in the phenol.mol2
(Figure 17) and phenol_resp.prepc (Figure 19) are different.

(4) The AMBER Frcmod file phenol_resp.frcmod can be loaded immediately followed by
opening the AMBER Prepc file through the menu FileOpen. If the AMBER Frcmod
has not been loaded in this step, it can be loaded later by clicking on the menu
ProtocolAMBER FrcmodLoad AMBER Frcmod (Figure 20).
 VFFDT Manual 25

Figure 20. Load the additional AMBER Frcmod file via clicking on the menu
ProtocolAMBER FrcmodLoad AMBER Frcmod.

(5) If both AMBER Prepc file phenol_resp.prepc and Frcmod file phenol_resp.frcmod
have been loaded already, users can directly view the parameters in the table by clicking
on the menu ProtocolFF for the Whole General Small Molecule (Figure 21).

VFFDT Manual 26
VFFDT Manual 27

 VFFDT Manual 28

Figure 21. The AMBER atomic type, bond parameters, angle parameters, dihedral
parameters and improper parameters can be viewed in the table. Clicking on each entry in
the table, then all the corresponding atoms will be highlighted in the VFFDT viewer
window.

(6) If AMBER atomic type of the carbon atom attached to the hydroxyl group in the phenol
molecule is hypothesized as cw instead of ca due to its chemical environment. There
are two panels for users to alter the AMBER atomic type. One panel is titled Atom
Property, and the other is titled All Related Force Field Parameters (Figure 22).
VFFDT Manual 29

 VFFDT Manual 30

Figure 22. Two methods for users to change the AMBER atomic type. The first method is
to select the atom in the VFFDT viewer window, right click the mouse, and change
AMBER atomic type. The second method is to double click the cell, modify AMBER
 VFFDT Manual 31

atomic type and then press the key Enter.

(7) Once the AMBER atomic type is modified, a new AMBER atomic type cw will be
defined in the AMBER Frcmod file, but all the cw related parameters will be copied from
ca by default. The updated AMBER Frcmod can be viewed in the panel View AMBER
Frcmod via clicking on the menu ProtocolAMBER FrcmodView AMBER
Frcmod (Figure 23).

Figure 23. View the updated AMBER Frcmod after modifying the AMBER atomic type. It
can be seen that a new AMBER atomic type cw is added.
(8) If the chemical environment of cw is hypothesized to be different from ca, cw related
bond parameters (such as ca-cw) and angle parameters (such as ca-cw-ca) can be re-derived
from the Seminario method based on the previous tutorial (Tutorial 1 and 2). Assuming
that the Gaussian output with keyword #p b3lyp/6-31g* opt freq=noraman was prepared
in advance, the Gaussian output will be loaded in another VFFDT viewer window by
clicking on the VFFDT program icon (Figure 24).
 VFFDT Manual 32

Figure 24. Clicking on the menu ProtocolFF for the Whole General Small
Molecule. The panel titled All Related Force Field Parameters can assign the
 VFFDT Manual 33

AMBER GAFF atomic type automatically and derive all the parameters for the bond and
angle term by Seminario method with frequency scaling factor 1.062 for PM6, which is
from the Computational Chemistry Comparison and Benchmark DataBase (CCCBDB) on
the website (http://cccbdb.nist.gov/vibscalejust.asp)
(9) Change the AMBER atomic type of atom C1 from ca to cw via double-click, and then
click on the command Statistics on the panel All Related Force Field Parameters.
Finally click on the command Map Parameters in textbox to Molecule (Figure 25) to
map the averaged parameter given by Seminario method in the textbox to the molecule in
the VFFDT window.

 VFFDT Manual 34

Figure 25. Double click the AMBER atomic type of atom C1 and alter the AMBER atomic
type from ca to cw, then click on the Command Statistics and open the panel titled
Statistics For Parameter, and finally click on the command Map Parameters in
textbox to Molecule.
(10) Copy the specific atom related parameters from one molecule to another molecule. Select
the atom with AMBER atomic type cw in the VFFDT viewer titled phenol.out and
click on the menu EditCopy/Paste Atom InfoCopy/Paste Atom Related
ParametersCopy Atom Related Parameters, and then select the target atom with
AMBER atomic type cw in another VFFDT viewer window titled phenol_resp.prepc
and click on the menu EditCopy/Paste Atom InfoCopy/Paste Atom Related
ParametersPaste Bond and Angle Parameters. In this step, only bond and angle
related parameters derived from Seminario method will apply to the molecule titled
phenol_resp.prepc (Figure 26).
VFFDT Manual 35
 VFFDT Manual 36

Figure 26. The parameter derived with Seminario method is copied from the window titled
phenol.out and is pasted to the window titled phenol_resp.prepc. Note: only selected
atom related parameters will be copied and pasted.
(11) After copy and paste in the previous step, the updated parameter can be viewed via clicking
on the menu ProtocolAMBER FrcmodView AMBER Frcmod (Figure 27).
 VFFDT Manual 37

Figure 27. Panel titled View AMBER Frcmod shows that parameters have been
updated successfully after the copy/paste operation.
(12) The updated parameters can be saved via clicking on the menu ProtocolAMBER
FrcmodSave AMBER Frcmod. Alternatively, both AMBER Frcmod and AMBER
Prepc can be saved subsequently by clicking on the menu FileSave. In this step, two
files phenol_resp_modified.prepc and phenol_resp_modified.frcmod can be created.
 VFFDT Manual 38

Figure 28. The menu FileSave is used to save the AMBER Prepc and Frcmod files.
(13) The two files phenol_resp_modified.prepc and phenol_resp_modified.frcmod
obtained in the previous step will be used in the tleap or xleap in Ambertools.

Figure 29. Script for tleap or xleap to generate the AMBER topology and coordinate file.

5. Contact Information

If there is any question or problem about VFFDT, please contact Dr. Fu Lin via the email:
lin1449@126.com.
 VFFDT Manual 39

6. Reference

1. Lin et al., Systematic derivation of Force Field Parameters Applicable to Zinc J. Chem.
Theory Comput. 2010, 6, 1852-1870.
2. Lin et al., Visual Force Field Derivation Toolkit (VFFDT): A New software for Preparing
AMBER Force Field Parameters for Metal-Containing Molecular Systems. J. Chem. Inf.
Model. 2016. (Published online, DOI: 10.1021/acs.jcim.5b00687)