CONFLEX Tutorials

[Structure optimization and vibrational analysis]

Structure optimization and vibrational analysis of a molecule by CONFLEX are explained.

[Execution of structure optimization and vibrational analysis]

By using Cyclohexane, how to execute structure optimization and vibrational analysis is explained.
First, prepare a structure file of Cyclohexane molecule in MDL-MOL format as Cyclohexane.mol. The Cyclohexane.mol is in Sample_Files folder in the folder installed CONFLEX (Sample_Files\CONFLEX\optimization_and_search\Cyclohexane.mol).

Cyclohexane.mol file

cyclohexane.mol
  • A1: The number of atoms (up to 999)
  • A2: The number of bonds (up to 999)
  • A3: Currently not use
  • A4: Currently not use
  • A5: Existence of optically active center (0: not have, 1: have) : Currently not use
  • B1: Cartesian coordinates and symbols of atoms
  • B2: Physical property list of atoms (Isotopes, charge, stereocenter, and so on set. In general, only charge and stereocenter are required.)
  • C1: Information on bonds between atoms (Information on adjacent bonds when atoms are the center is indicated. The bonding state, three-dimensional state, bonding topology and the like are indicated. Usually only information on bonds between adjacent atoms, bonding state and three-dimensional state are required.
  • D1: This indicates that atomic conformation has been completed and is necessary information.

[Execution by Interface]

Open the Cyclohexane.mol file by CONFLEX Interface.

Opt Interface Cyclohexane

Select [CONFLEX] in Calculation menu, and click Submit in the calculation setting dialog displayed. The calculation of molecular structure optimization and normal mode analysis will be performed.

Interface Basic

[Execution by command line]

Store the Cyclohexane.mol in a folder, and execute below command. A calculation will start.

C:\CONFLEX\bin\flex9a_win_x64.exe   -par   C:\CONFLEX\par   Cyclohexane
enter

The above command is for Windows OS. For the other OS, please refer to [How to execute CONFLEX].

When there is no an ini file in the folder, the calculation of molecular structure optimization and normal mode analysis will be performed in default setting.
In this case, the calculation is the same as when you prepared Cyclohexane.ini file that describes [MMFF94S OPT=NEWTON OPTBY=ENERGY] in the folder.

[Output files]

After the calculation finished, three files shown below are outputted.

Cyclohexane-F.mol

The optimized structure is outputted in this file in MDL-MOL format. The file format matches the input structure file.

Cyclohexane.mol
CONFLEX 20090414283D 1   1.00000    -3.56094     0                            
D3D ,E =   -3.561, G = 6.035E-11, M(0)      MMFF94S(2010-12-04HG)               
 18 18  0     0               999 V2000
   -1.2627    0.7290    0.2258 C   0  0  0  0  0     
    0.0000    1.4580   -0.2258 C   0  0  0  0  0     
   -1.2627   -0.7290   -0.2258 C   0  0  0  0  0     
   -2.1462    1.2391   -0.1742 H   0  0  0  0  0     
   -1.3365    0.7716    1.3195 H   0  0  0  0  0     
   -0.0000    2.4782    0.1742 H   0  0  0  0  0     
    0.0000    1.5433   -1.3195 H   0  0  0  0  0     
    0.0000   -1.4580    0.2258 C   0  0  0  0  0     
   -2.1462   -1.2391    0.1742 H   0  0  0  0  0     
   -1.3365   -0.7716   -1.3195 H   0  0  0  0  0     
    0.0000   -2.4782   -0.1742 H   0  0  0  0  0     
    0.0000   -1.5433    1.3195 H   0  0  0  0  0     
    1.2627   -0.7290   -0.2258 C   0  0  0  0  0     
    2.1462   -1.2391    0.1742 H   0  0  0  0  0     
    1.3365   -0.7716   -1.3195 H   0  0  0  0  0     
    1.2627    0.7290    0.2258 C   0  0  0  0  0     
    1.3365    0.7716    1.3195 H   0  0  0  0  0     
    2.1462    1.2391   -0.1742 H   0  0  0  0  0     
  2  1  1  0     0
  3  1  1  0     0
  1  4  1  0     0
  1  5  1  0     0
  2  6  1  0     0
  2  7  1  0     0
  2 16  1  0     0
  3  8  1  0     0
  3  9  1  0     0
  3 10  1  0     0
 11  8  1  0     0
 12  8  1  0     0
 13  8  1  0     0
 14 13  1  0     0
 13 15  1  0     0
 16 13  1  0     0
 16 17  1  0     0
 16 18  1  0     0
M  END

Cyclohexane.bsf

Atomic coordinates of the optimized structure and energy value, and so on are outputted in this file.

999.9 6 0 6  0 1  0  010.00  1.00E-06  1.00E-06   0   0 25.000010001100000000000
Cyclohexane: Cyclohexane.mol                                                    
D3D ,E =   -3.561, G = 6.035E-11, M(0)      MMFF94S(2010-12-04HG)               
18 18
 0.00000   0.00000   0.00000   0.00000   0.00000   0.00000   0.00000   0.00000
 0.00000   0.00000   0.00000   0.00000   0.00000   0.00000   0.00000   0.00000
 0.00000   0.00000
-1.262673724   0.729005014   0.225782342  6  0 12   2   3   4   5   0   0   1
 0.000000000   1.458010029  -0.225782342  6  0 12   1   6   7  16   0   0   2
-1.262673724  -0.729005014  -0.225782342  6  0 12   1   8   9  10   0   0   3
-2.146189104   1.239102857  -0.174187977  1  0  1   1   0   0   0   0   0   4
-1.336507200   0.771632792   1.319462875  1  0  1   1   0   0   0   0   0   5
-0.000000000   2.478205714   0.174187977  1  0  1   2   0   0   0   0   0   6
 0.000000000   1.543265583  -1.319462875  1  0  1   2   0   0   0   0   0   7
 0.000000000  -1.458010029   0.225782342  6  0 12   3  11  12  13   0   0   8
-2.146189104  -1.239102857   0.174187977  1  0  1   3   0   0   0   0   0   9
-1.336507200  -0.771632792  -1.319462875  1  0  1   3   0   0   0   0   0  10
 0.000000000  -2.478205714  -0.174187977  1  0  1   8   0   0   0   0   0  11
 0.000000000  -1.543265583   1.319462875  1  0  1   8   0   0   0   0   0  12
 1.262673724  -0.729005014  -0.225782342  6  0 12   8  14  15  16   0   0  13
 2.146189104  -1.239102857   0.174187977  1  0  1  13   0   0   0   0   0  14
 1.336507200  -0.771632792  -1.319462875  1  0  1  13   0   0   0   0   0  15
 1.262673724   0.729005014   0.225782342  6  0 12   2  13  17  18   0   0  16
 1.336507200   0.771632792   1.319462875  1  0  1  16   0   0   0   0   0  17
 2.146189104   1.239102857  -0.174187977  1  0  1  16   0   0   0   0   0  18

Cyclohexane.bso

This file has force field parameters were used the calculation, energies of each interaction as well as thermodynamic quantities, frequencies, and vibrational modes obtained by the normal mode analysis.

cyclohexane.bso
  • (A-1): Name of force field used
  • (A-2): Information of atom type assigned to atoms composing of input molecule
  • (A-3): Function of bond stretching interaction and its parameters in the force field used
  • Functions of other interactions and their parameters are shown after A-3.
cyclohexane.bso-2
  • (A-4): Initial coordinates and serial numbers of atoms
  • (A-5): Atom type assigned to atoms
  • (A-6): Bond information
  • (A-7): Energy gradient with respect to input structure
cyclohexane.bso-3
  • (A-8): Inertia moment and dipole moment of input structure
  • (A-9): Steric energies of each interaction function term for input structure
cyclohexane.bso-4
  • (A-10)：Process of structure optimization by Newton-Raphson method
  • (A-11)：Structural optimization has converged.
  • (A-12)：Final eigenvalues. Assuming that the eigenvalues less than the absolute value of cut-off are “0”, the number of eigenvalue of zero is 5 in linear molecules, and that is 6 in other molecules.
cyclohexane.bso-5
  • (A-13): Structure information and energies of each interactions in input molecule defined by the force field used.
cyclohexane.bso-6
  • (A-14): The partition function amount relating to internal energy, enthalpy, entropy, Gibbs free energy and constant pressure heated capacity are calculated taking into account the details of the thermodynamic functions, the temperature designated and the symmetry of the optimized structure.
  • (A-15): The number of imaginary, zero, and real frequencies. You should check that optimized structure has 6 zero-frequencies and doesn't have any imaginary frequencies.
cyclohexane.bso-7
  • (A-16): Frequencies and vibrational modes. The vibrational modes show as displacement vectors in Cartesian coordinate system. By using a keyword, the vectors can also be shown in an internal coordinate system.

[Visualization of calculation results]

[If you executed the calculation by using Interface]

After submitting a job, Job Manager is appeared at bottom of CONFLEX Interface. Job Manager shows a state of the job.

Opt Job Manager

Confirm the state of the job is “Finished”, and double-click the row of the job (red frame part).

Cyclohexane.bso will automatically open, and the optimized structure will be displayed. The Cyclohexane.bso file is in the folder contained the input files.

Interface Opt

Select [Vibration] in View menu, you can see atomic displacement vectors due normal vibrations.

Interface NMode

* You can change magnitude of the arrows by the tool bar appeared by selecting [Controller] in View menu.

[If you executed the calculation by using command line]

Open either Cyclohexane-F.mol or Cyclohexane.bso file by CONFLEX Interface, you can see the optimized structure. These files are in the folder contained the input files.

Interface Opt-2

If you opened Cyclohexane.bso, select [Vibration] in View menu, you can see atomic displacement vectors due normal vibrations.

Interface NMode-2

* You can change magnitude of the arrows by the tool bar appeared by selecting [Controller] in View menu.

[Calculation with solvent effects]

Introduce solvent effects by GB/SA model

When compounds are synthesized and the structure and physical property values are measured in chemical experiments, almost all experiments are conducted in solution. Therefore, when analyzing phenomena obtained experimentally using molecular calculations, as long as the experiment in question involves handling a compound in a solution, the calculations must also take into account the state of the solution. However, the usual molecular force fields and the like are constructed as if the structure of the compound is in the gas phase and the contribution of the solvent is ‘not’ taken into consideration. Although calculations which deploy a great deal of solvent molecules should be carried out around the solute, in this case, the degree of freedom commensurate with the number of solvent molecules increases and the calculation time increases considerably.

Research on the introduction of the solvent effect using a continuous dielectric model has long been carried out in the field of molecular calculations in order to eliminate this problem. When CONFLEX is used, a GB/SA model which is a continuous dielectric model and which has been most widely used in calculating molecular dynamics is used. Computation of the structural optimization, vibrational analysis and the solvent degree of freedom energy which incorporate the solvent effect can be carried out. Furthermore, in the present version, the force field used is MMFF94s and octanol is considered as the solvent.

What is GB/SA model ?

The GB/SA model involves calculating the electrostatic contribution by the solvent using the generalized Born (Generalized Born, GB) equation and is a model wherein the non-electrostatic contribution is computed based on the solvent-accessible surface area, (SA). The amount of increase in energy caused by the solvent is expressed as

GB Eq.1

The electrostatic term becomes

GB Eq.2

using the GB equation and the non-electrostatic term is calculated as

GB Eq.3

Here, the qi is a charge of atom i, the rij is distance between atoms i and j, the αij and Dij are values obtained by effective Born radius, the σkis a surface tension coefficient, and the SAk is a solvent-accessible surface area of atom k.
In CONFLEX9 and later, [SA=IGNORE] keyword has been added to ignore the non-electrostatic term in the calculation. If a structure optimization with solvent effects is not converge, please add this keyword to the calculation setting.

Calculation with GB/SA model

We use a zwitterionic glycine dimer.

Gly

Structure data of the zwitterionic glycine dimer (gly2.mol)

gly2.mol


 17 16  0  0  0  0  0  0  0  0999 V2000
   -1.2219    0.9765   -2.1504 N   0  3  0  0  0  0  0  0  0  0  0  0
    0.2781    0.9765   -2.1504 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.6496    2.0256   -2.1504 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.7803    0.2658   -0.9176 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9679    0.1552   -0.7258 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1098   -0.2537   -0.0165 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.3728   -0.9366    1.1681 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9911   -0.2372    1.7741 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8018   -1.4089    1.9892 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6088   -2.0256    3.0592 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9679   -1.1835    1.5993 O   0  5  0  0  0  0  0  0  0  0  0  0
   -1.5708    0.4839   -3.0034 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5698    0.4832   -1.2973 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5701    1.9618   -2.1504 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.6489    0.4518   -3.0592 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1047   -0.1611   -0.1772 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.9910   -1.8114    0.8658 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0      
  1 12  1  0      
  1 13  1  0      
  1 14  1  0      
  2  3  1  0      
  2  4  1  0      
  2 15  1  0      
  4  5  2  0      
  4  6  1  0      
  6  7  1  0      
  6 16  1  0      
  7  8  1  0      
  7  9  1  0      
  7 17  1  0      
  9 10  2  0      
  9 11  1  0      
M  END

[Execution by Interface]

Open the gly2.mol file by CONFLEX Interface.

Interface Gly Open

Select [CONFLEX] in Calculation menu, and click Detail Settings in the calculation setting dialog displayed.

CONFLEX Dialog

Next, in [Force Field] dialog on the detail setting dialog, select [GB/SA] in the pull-down menu of [Solvent Effect].

Force Field Dialog

When the calculation settings are complete, click Submit. The calculation will start.

[Execution by command line]

The calculation settings are defined by describing keywords in the gly2.ini file.

gly2.ini file

MMFF94S GBSA

[GBSA] means to execute calculation with solvent effects by GB/SA model.
[MMFF94S] means to use MMFF94s force field.

Store the two files of gly2.mol and gly2.ini in an one folder, and execute below command. The calculation will start. 

C:\CONFLEX\bin\flex9a_win_x64.exe   -par   C:\CONFLEX\par   gly2
enter

The above command is for Windows OS. For the other OS, please refer to [How to execute CONFLEX].

Calculation results

The structure optimized is shown below. How to visualize this, please refer to [Visualization of calculation results].

Final Structure

[Structure optimization with constraints]

In structure optimization process, all degrees of freedom of atoms are relaxed. However, structure optimization with constraints for fixing partial structures may be necessary in some cases, such as when you want to optimize only for unknown parts whose structure is partially known, or when you want to optimize while keeping certain structural parameters.
In CONFLEX, the structure optimization with the constraints can be performed by three methods described below.

It is also possible to perform conformational search with these methods.

* Constraint by pseudo force potential

It is possible to restrict a relaxation of partial structure by adding pseudo potential to structural parameters such as distance between two atoms, bond angle, dihedral angle, and so on.
Keywords for adding the pseudo potential to each structural parameter are as follows:

Structural parameter Keyword Explanation
Bond length PSEUDO_BOND=(I,J,STD,FK) The harmonic potential with the standard length STD (Å) and the force constant FK (kcal・mol-1・Å-2) adds to the atomic pair of I and J.
PSEUDO_HALF=(I,J,STD,FK) The half-harmonic potential with the standard length |STD| (Å) and the force constant FK (kcal・mol-1・Å-2) adds to the atomic pair of I and J. In case of STD>0, the energy increases as the distance between I-J becomes longer than STD. On the other hand, in case of STD<0, the energy increases as the distance between I-J becomes shorter than STD.
Valence angle PSEUDO_ANGL=(I,J,K,STD,FK) The harmonic potential with the standard angle STD (°) and the force constant FK (kcal・mol-1・rad-2) adds to the valence angle of I-J-K.
Dihedral angle PSEUDO_TORS=(I,J,K,L,STD,FK) The harmonic potential with the standard angle STD (°) and the force constant FK (kcal・mol-1・rad-2) adds to the dihedral angle of I-J-K-L.

Example calculation

This section explains a structure optimization of n-butane with trans conformation by using the pseudo potential for maintaining C-C-C-C dihedral angle to around 150.0.

Three dimensional structure of n-butane

n-butane

Structure data of n-butane (n-butane.mol)

n-butane.mol


 14 13  0  0  0  0  0  0  0  0999 V2000
   -1.1802   -1.5102    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.1388   -0.7487    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.1388    0.7487    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1802    1.5102    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9774   -2.6046    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7631   -1.2415    0.9093 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7637   -1.2413   -0.9088 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.7217   -1.0175   -0.9093 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.7223   -1.0177    0.9088 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7217    1.0175    0.9093 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7223    1.0177   -0.9088 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.9774    2.6046    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.7631    1.2415   -0.9093 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.7637    1.2412    0.9088 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  1  5  1  0
  1  6  1  0
  1  7  1  0
  2  3  1  0
  2  8  1  0
  2  9  1  0
  3  4  1  0
  3 10  1  0
  3 11  1  0
  4 12  1  0
  4 13  1  0
  4 14  1  0
M  END

[Execution by Interface]

Open the n-butane.mol file by CONFLEX Interface.

Interface n-butane

Select [CONFLEX] in Calculation menu, and click Detail Settings in the calculation setting dialog displayed.
Next, click Edit & Submit at bottom right in the detail setting dialog.

Interface Details

Add [PSEUDO_TORS=(1,2,3,4,150.0,100.0)] to the dialog displayed. By this keyword, the harmonic potential with the standard angle 150 (°) and the force constant 100.0 (kcal・mol-1・rad-2) adds to the dihedral angle of C-C-C-C.
When the calculation settings are complete, click Submit. The calculation will start.

Interface Edit Submit

[Execution by command line]

The calculation settings are defined by describing keywords in the n-butane.ini file.

n-butane.ini file

MMFF94S
PSEUDO_TORS=(1,2,3,4,150.0,100.0)

[MMFF94S] means to use MMFF94s force field.
[PSEUDO_TORS=(1,2,3,4,150.0,100.0)] means that the harmonic potential with the standard angle 150 (°) and the force constant 100.0 (kcal・mol-1・rad-2) adds to the dihedral angle of C-C-C-C.

Store the two files of n-butane.mol and n-butane.ini in an one folder, and execute below command. The calculation will start. 

C:\CONFLEX\bin\flex9a_win_x64.exe   -par   C:\CONFLEX\par   n-butane
enter

The above command is for Windows OS. For the other OS, please refer to [How to execute CONFLEX].

Calculation results

The larger the force constant value, the closer the dihedral angles of the optimized structure is to the STD value. Table 1 shows the dihedral angle of the structures optimized by using different settings of the force constant.

Table 1: Force constant and C-C-C-C dihedral angle of the optimized structure

Force constant (kcal・mol-1・rad-2) Dihedral angle (°)
10 168.6
100 153.4
1000 150.3

* Constraint by molecular object method

In case of a system consists of more than one molecule, CONFLEX can do that specified molecules are optimized and remaining ones are fixed.
In this calculation, it is necessary to set both “OPT=GROUP” and “MOL_GROUP=(I,N)” keywords. Here, N and I in MOL_GROUP keyword are a group number and atom number for the molecule to be optimized, respectively.

Example calculation

We optimize only water molecule in the system consists of α-D-glucose and water.

alpha-D-glucose

Structure data (aDglucose_H2O.mol)

aDglucose_H2O.mol
    

 27 26  0  0  0               999 V2000
   -0.5024    2.4148    0.6016 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8520   -1.0932   -0.5731 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.4519   -1.5744   -0.2774 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2020    1.2411   -0.1553 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1949    0.1125    0.1452 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1431    1.8092   -0.2200 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.5330   -1.9764    1.0847 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.8319   -0.9820   -0.1321 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6186    0.5024   -0.2701 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.5391   -0.5233   -0.5592 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2184    0.7799    0.1723 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5094   -0.5881   -0.0183 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.2794    2.9953    0.4978 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.6445   -2.4621   -0.8896 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2535    1.5201   -1.2154 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2141   -0.1177    1.2184 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.0267    1.3889   -0.1951 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0183   -2.7768    1.1469 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.6839   -1.4193    0.7318 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6702    0.7196   -1.3421 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9791    1.3731    0.2851 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.6027   -0.3262   -1.6358 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.3472    0.6668    1.2558 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0727   -1.3725   -0.4004 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3106    0.8234   -2.7522 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3290    0.0085   -2.2451 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9697    0.7822   -3.4490 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  4  1  0  0  0  0
  1 13  1  0  0  0  0
  2  3  1  0  0  0  0
  2  5  1  0  0  0  0
  3  7  1  0  0  0  0
  3 10  1  0  0  0  0
  3 14  1  0  0  0  0
  4  5  1  0  0  0  0
  4 11  1  0  0  0  0
  4 15  1  0  0  0  0
  5  9  1  0  0  0  0
  5 16  1  0  0  0  0
  6 11  1  0  0  0  0
  6 17  1  0  0  0  0
  7 18  1  0  0  0  0
  8 10  1  0  0  0  0
  8 19  1  0  0  0  0
  9 12  1  0  0  0  0
  9 20  1  0  0  0  0
  9 21  1  0  0  0  0
 10 11  1  0  0  0  0
 10 22  1  0  0  0  0
 11 23  1  0  0  0  0
 12 24  1  0  0  0  0
 25 26  1  0  0  0  0
 25 27  1  0  0  0  0
M  END

[Execution by Interface]

Open the aDglucose_H2O.mol file by CONFLEX Interface.

Interface Glucose

Select [CONFLEX] in Calculation menu, and click Detail Settings in the calculation setting dialog displayed.
Next, click Edit & Submit at bottom right in the detail setting dialog.

Add keywords of [OPT=GROUP], [MOL_GROUP=(25,1)], and [NOSYMMETRY] to the dialog displayed.

Edit Submit dialog

By adding the [OPT=GROUP] and [MOL_GROUP=(25,1)], only the water having the atom with serial number of 25 will be optimized. [NOSYMMETRY] means that any coordinate transformations do not apply to the optimized structure. This setting provides that the coordinates of α-D-glucose are unchanged from input data.

When the calculation settings are complete, click Submit. The calculation will start.

[Execution by command line]

The calculation settings are defined by describing keywords in the aDglucose_H2O.ini file.

aDglucose_H2O.ini file

MMFF94S
OPT=GROUP
MOL_GROUP=(25,1)
NOSYMMETRY

[MMFF94S] means to use MMFF94s force field.
By adding the [OPT=GROUP] and [MOL_GROUP=(25,1)], only the water having the atom with serial number of 25 will be optimized.
[NOSYMMETRY] means that any coordinate transformations do not apply to the optimized structure. This setting provides that the coordinates of α-D-glucose are unchanged from input data.

Store the two files of aDglucose_H2O.mol and aDglucose_H2O.ini files in an one folder, and execute below command. The calculation will start. 

C:\CONFLEX\bin\flex9a_win_x64.exe   -par   C:\CONFLEX\par   aDglucose_H2O
enter

The above command is for Windows OS. For the other OS, please refer to [How to execute CONFLEX].

Calculation results

The structure optimized only water molecule is shows below. How to visualize this, please refer to [Visualization of calculation results].

Optimized Glucose

* Constraint by freezing atomic coordinates

This section explains how to fix atomic coordinates. In order to fix the atomic coordinates, you should use “FIXED_ATOMS=(I,J,...)” keyword. Alternatively, specifying the atoms to be optimized by “OPTMZD_ATOMS=(I,J,...)” keyword, the other atoms can be fixed. I and J are serial number of atoms. When you use a hyphen like “K-L”, you can set for atoms from K to L.
Both “FIXED_ATOMS=” and “OPTMZD_ATOMS=” keywords cannot be used at the same time. When you use both the keywords, the keywords will be ignored.

Example calculation

This section explains how to perform a molecular structure optimization of Captopril under freezing the structure of 5-membered ring.

Captopril

Structure data (Captopril.mol)

Captopril.mol


 29 29  0  0  0  0  0  0  0  0999 V2000
   -2.3252   -1.0023    1.2229 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6239   -0.4662   -0.4492 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0498   -0.4139   -0.1391 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.6884   -1.2552   -1.2306 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5887   -2.2017   -1.6972 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3763   -1.8473   -0.8534 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4559   -1.0423    1.6461 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3170   -1.4796    1.9618 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.2831    0.5566   -0.3768 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7272    0.3117   -0.7399 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5188    1.6023   -0.5751 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0725    1.6553   -0.0222 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.3057   -0.7585    0.1764 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4156    2.1604    1.1489 S   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4462    0.6256   -0.1090 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0306   -0.6102   -2.0707 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5838   -1.8050   -0.8634 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8868   -3.2604   -1.5267 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3835   -2.0978   -2.7862 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.5587   -1.9230   -1.4524 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2408   -2.5317    0.0138 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7170   -1.8038    2.7862 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.7909   -0.0300   -1.7972 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.5838    1.4203   -0.8424 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.0958    2.3847   -1.2441 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.3709   -0.9399   -0.0905 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.7276   -1.7018    0.0555 H   0  0  0  0  0  0  0  0  0  0  0  0
    2.2416   -0.4159    1.2334 H   0  0  0  0  0  0  0  0  0  0  0  0
    3.1721    3.2604    0.9861 H   0  0  0  0  0  0  0  0  0  0  0  0
  3  1  1  0
  1  7  2  0
  1  8  1  0
  2  3  1  0
  2  6  1  0
  2  9  1  0
  3  4  1  0
  3 15  1  0
  4  5  1  0
  4 16  1  0
  4 17  1  0
  5  6  1  0
  5 18  1  0
  5 19  1  0
  6 20  1  0
  6 21  1  0
  8 22  1  0
  9 10  1  0
  9 12  2  0
 10 11  1  0
 10 13  1  0
 10 23  1  0
 11 14  1  0
 11 24  1  0
 11 25  1  0
 13 26  1  0
 13 27  1  0
 13 28  1  0
 14 29  1  0
M  END

[Execution by Interface]

Open the Captoril.mol file by CONFLEX Interface.
Interface Captopril

Select [CONFLEX] in Calculation menu, and click Detail Settings in the calculation setting dialog displayed.
Next, click Edit & Submit at bottom right in the detail setting dialog.

Add [FIXED_ATOMS=(2-6)] keyword to the dialog displayed.

Captopril Edit Submit

By adding the [FIXED_ATOMS=(2-6)], you can optimize the Captopril molecule under freezing the structure of 5-membered ring.
Alternatively, you can set the constraint by using [FIXED_ATOMS=(2,3,4,5,6)] or [OPTMZD_ATOMS=(1,7-29)] keyword.

When the calculation settings are complete, click Submit. The calculation will start.

[Execution by command line]

The calculation settings are defined by describing keywords in the Captoril.ini file.

Captoril.ini file

MMFF94S
FIXED_ATOMS=(2-6)

[MMFF94S] means to use MMFF94s force field.
By adding the [FIXED_ATOMS=(2-6)], you can optimize the Captopril molecule under freezing the structure of 5-membered ring. Alternatively, you can set the constraint by using [FIXED_ATOMS=(2,3,4,5,6)] or [OPTMZD_ATOMS=(1,7-29)] keyword.

Store the two files of Captoril.mol and Captoril.ini files in an one folder, and execute below command. The calculation will start. 

C:\CONFLEX\bin\flex9a_win_x64.exe   -par   C:\CONFLEX\par   Captoril
enter

The above command is for Windows OS. For the other OS, please refer to [How to execute CONFLEX].

Calculation results

The structure of Captoril optimized under the constraint is shows below. How to visualize this, please refer to [Visualization of calculation results].

Pertial Opt

Structure data (Captopril-F.mol)

Captopril.mol

NONE,E =   11.183, G = 4.571E-08, M(0)      MMFF94S(2010-12-04HG)
 29 29  0     0               999 V2000
   -2.4430   -0.8871    1.2669 C   0  0  0  0  0
   -0.6239   -0.4662   -0.4492 N   0  0  0  0  0
   -2.0498   -0.4139   -0.1391 C   0  0  0  0  0
   -2.6884   -1.2552   -1.2306 C   0  0  0  0  0
   -1.5887   -2.2017   -1.6972 C   0  0  0  0  0
   -0.3763   -1.8473   -0.8534 C   0  0  0  0  0
   -3.5862   -0.9722    1.6925 O   0  0  0  0  0
   -1.4082   -1.2283    2.0621 O   0  0  0  0  0
    0.2367    0.5531   -0.1333 C   0  0  0  0  0
    1.7337    0.3050   -0.3298 C   0  0  0  0  0
    2.5093    1.6332   -0.4281 C   0  0  0  0  0
   -0.1962    1.6320    0.2729 O   0  0  0  0  0
    2.2822   -0.6428    0.7379 C   0  0  0  0  0
    2.9575    2.4405    1.1463 S   0  0  0  0  0
   -2.3907    0.6266   -0.2018 H   0  0  0  0  0
   -2.9966   -0.6195   -2.0696 H   0  0  0  0  0
   -3.5750   -1.8028   -0.8948 H   0  0  0  0  0
   -1.8649   -3.2542   -1.5802 H   0  0  0  0  0
   -1.3807   -2.0322   -2.7601 H   0  0  0  0  0
    0.5549   -1.9446   -1.4157 H   0  0  0  0  0
   -0.3095   -2.4758    0.0407 H   0  0  0  0  0
   -1.8251   -1.4249    2.9265 H   0  0  0  0  0
    1.8469   -0.1748   -1.3104 H   0  0  0  0  0
    3.4547    1.4484   -0.9511 H   0  0  0  0  0
    1.9539    2.3588   -1.0328 H   0  0  0  0  0
    3.3735   -0.7125    0.6778 H   0  0  0  0  0
    1.8903   -1.6560    0.6140 H   0  0  0  0  0
    2.0042   -0.3222    1.7476 H   0  0  0  0  0
    3.3407    3.6094    0.6130 H   0  0  0  0  0
  3  1  1  0     0
  1  7  2  0     0
  1  8  1  0     0
  2  3  1  0     0
  2  6  1  0     0
  2  9  1  0     0
  3  4  1  0     0
  3 15  1  0     0
  4  5  1  0     0
  4 16  1  0     0
  4 17  1  0     0
  5  6  1  0     0
  5 18  1  0     0
  5 19  1  0     0
  6 20  1  0     0
  6 21  1  0     0
  8 22  1  0     0
  9 10  1  0     0
  9 12  2  0     0
 10 11  1  0     0
 10 13  1  0     0
 10 23  1  0     0
 11 14  1  0     0
 11 24  1  0     0
 11 25  1  0     0
 13 26  1  0     0
 13 27  1  0     0
 13 28  1  0     0
 14 29  1  0     0
M  END