CONFLEX Tutorials

CD/UV spectrum analysis

Dexmedetomidine is a medetomidine activator (D-form) having an imidazole skeleton and is a high central α2 adrenaline receptor agonist with high strength and selectivity. It inhibits stimulus transfer of the sympathetic nerve by stimulating the central nerve a2 receptor and has a sedative effect. Furthermore, this molecule has the simplest optical activity.
This section explains how to perform CD/UV spectrum calculation using the dexmedetomidine molecule.

Structural formula of dexmedetomidine: Precedex®

Precedex

Structure data of dexmedetomidine (R-form) (Dexmedetomidine.mol)

Dexmedetomidine


 31 32  0  0  0                 1 V2000
   -1.0778   -1.6715    0.6897 C   0  0  0  0  0
   -2.0603   -2.6647    1.0836 N   0  0  0  0  0
   -2.4168   -2.2186    2.4226 C   0  0  0  0  0
   -1.8248   -1.1779    2.8306 N   0  0  0  0  0
   -0.9540   -0.8156    1.7107 C   0  0  0  0  0
   -0.0612    0.3840    1.7794 C   0  0  0  0  0
    0.6530    0.5305    0.4721 C   0  0  0  0  0
    1.6443   -0.4148    0.0972 C   0  0  0  0  0
    2.3211   -0.2864   -1.1434 C   0  0  0  0  0
    2.0041    0.7900   -2.0119 C   0  0  0  0  0
    1.0134    1.7374   -1.6414 C   0  0  0  0  0
    0.3382    1.6082   -0.3982 C   0  0  0  0  0
   -0.8947    1.6284    2.0582 C   0  0  0  0  0
   -0.7060    2.6067   -0.0050 C   0  0  0  0  0
    0.6790    2.8690   -2.5617 C   0  0  0  0  0
   -0.5680   -1.6802   -0.2851 H   0  0  0  0  0
   -1.9104   -3.6810    0.8775 H   0  0  0  0  0
   -3.1582   -2.7716    3.0179 H   0  0  0  0  0
    0.6828    0.2465    2.5956 H   0  0  0  0  0
    1.8873   -1.2500    0.7705 H   0  0  0  0  0
    3.0881   -1.0203   -1.4318 H   0  0  0  0  0
    2.5261    0.8903   -2.9749 H   0  0  0  0  0
   -0.9541    1.8063    3.1554 H   0  0  0  0  0
   -1.9247    1.4948    1.6581 H   0  0  0  0  0
   -0.4306    2.5163    1.5733 H   0  0  0  0  0
   -1.1426    2.3320    0.9812 H   0  0  0  0  0
   -0.2528    3.6205    0.0707 H   0  0  0  0  0
   -1.5176    2.6296   -0.7662 H   0  0  0  0  0
   -0.1300    3.4917   -2.1188 H   0  0  0  0  0
    1.5781    3.5043   -2.7251 H   0  0  0  0  0
    0.3338    2.4705   -3.5419 H   0  0  0  0  0
  1  2  1  0  0  0
  1  5  2  0  0  0
  1 16  1  6  0  0
  2  3  1  1  0  0
  2 17  1  0  0  0
  3  4  2  0  0  0
  3 18  1  1  0  0
  4  5  1  6  0  0
  5  6  1  0  0  0
  6  7  1  6  0  0
  6 13  1  0  0  0
  6 19  1  1  0  0
  7  8  2  0  0  0
  7 12  1  6  0  0
  8  9  1  6  0  0
  8 20  1  1  0  0
  9 10  2  0  0  0
  9 21  1  0  0  0
 10 11  1  0  0  0
 10 22  1  6  0  0
 11 12  2  0  0  0
 11 15  1  6  0  0
 12 14  1  0  0  0
 13 23  1  1  0  0
 13 24  1  0  0  0
 13 25  1  0  0  0
 14 26  1  1  0  0
 14 27  1  0  0  0
 14 28  1  6  0  0
 15 29  1  0  0  0
 15 30  1  0  0  0
 15 31  1  6  0  0
M  END

Conformation search

[Execution by Interface]

Open the Dexmedetomidin.mol file by CONFLEX Interface.

Interface Dexmedetomidin

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

Basic Settings

Select [Conformation Search] in the pull-down menu of [Calculation Type:] in [General Settings] dialog on the detail setting dialog. General Settings

Edit the value of [Search Limit:] to 50.0 in [Conformation Search] dialog on the detail setting dialog.
When the calculation settings are complete, click Edit & Submit. Conformation Search

Add [PRECHK] to the dialog displayed, and click Submit. The calculation will start. Edit and Submit

[Execution by command line]

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

Dexmedetomidin.ini file

MMFF94S CONFLEX PRECHK SEL=50.0
  • [MMFF94S] means to use MMFF94s force field.
  • [CONFLEX] means to perform a conformation search.
  • [SEL=50.0] means to set a search limit to 50.0 kcal/mol.

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

C:\CONFLEX\bin\flex9a_win_x64.exe   -par   C:\CONFLEX\par   Dexmedetomidinenter

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

Calculation results

We can get 6 conformers from the conformation search.

No.ID Conf ID. Steric E (kcal/mol) ΔE (kcal/mol) Distribution (%)
R1 2 48.8457 0 47.0162
R2 5 49.1525 0.3068 28.0111
R3 3 49.2567 0.411 23.4962
R4 1 51.2498 2.4041 0.8129
R5 4 51.3723 2.5266 0.6611
R6 6 54.6699 5.8242 0.0025

CD/UV spectrum calculation

CD/UV spectrum calculations for the conformers are performed. Structure data of R1-R6 conformers are described in Dexmedetomidine.sdf in MDL-MOL file format.
Here, we extract structure data of the R1 conformer from Dexmedetomidine.sdf file and save as Dexmedetomidine_R1.mol.

Structure data of R1 conformer (Dexmedetomidine_R1.mol)

Dexmedetomidine                                                                 
  CONFLEX 20120911103D 1   1.00000    48.84570     2                            
C1  ,E =      48.846, G = 0.585E-07, P =  47.0162, M( 0), IFN =00000001-00000002
 31 32  0     0                 1 V2000
   -2.0874   -0.9516   -1.0953 C   0  0  0  0  0     
   -3.2087   -0.3537   -1.5970 N   0  0  0  0  0     
   -3.6187    0.5800   -0.6906 C   0  0  0  0  0     
   -2.8252    0.6169    0.3538 N   0  0  0  0  0     
   -1.8462   -0.3288    0.1149 C   0  0  0  0  0     
   -0.7355   -0.5857    1.0969 C   0  0  0  0  0     
    0.5101    0.0794    0.5067 C   0  0  0  0  0     
    0.5314    1.4826    0.3608 C   0  0  0  0  0     
    1.6413    2.1406   -0.1565 C   0  0  0  0  0     
    2.7595    1.4107   -0.5382 C   0  0  0  0  0     
    2.7854    0.0130   -0.4098 C   0  0  0  0  0     
    1.6575   -0.6664    0.1168 C   0  0  0  0  0     
   -1.0377   -0.1065    2.5179 C   0  0  0  0  0     
    1.6676   -2.1687    0.2694 C   0  0  0  0  0     
    4.0321   -0.7132   -0.8424 C   0  0  0  0  0     
   -1.5600   -1.7306   -1.6269 H   0  0  0  0  0     
   -3.6565   -0.5595   -2.4790 H   0  0  0  0  0     
   -4.4935    1.1972   -0.8447 H   0  0  0  0  0     
   -0.6109   -1.6715    1.1573 H   0  0  0  0  0     
   -0.3396    2.0732    0.6439 H   0  0  0  0  0     
    1.6304    3.2216   -0.2630 H   0  0  0  0  0     
    3.6185    1.9431   -0.9407 H   0  0  0  0  0     
   -1.9187   -0.6210    2.9181 H   0  0  0  0  0     
   -1.2403    0.9691    2.5673 H   0  0  0  0  0     
   -0.1934   -0.3152    3.1844 H   0  0  0  0  0     
    1.5390   -2.4397    1.3225 H   0  0  0  0  0     
    0.8650   -2.6129   -0.3286 H   0  0  0  0  0     
    2.5987   -2.6334   -0.0623 H   0  0  0  0  0     
    3.8018   -1.4182   -1.6475 H   0  0  0  0  0     
    4.7912   -0.0217   -1.2241 H   0  0  0  0  0     
    4.4752   -1.2463    0.0048 H   0  0  0  0  0     
  1  2  1  0     0
  1  5  2  0     0
  1 16  1  6     0
  2  3  1  1     0
  2 17  1  0     0
  3  4  2  0     0
  3 18  1  1     0
  4  5  1  6     0
  5  6  1  0     0
  6  7  1  6     0
  6 13  1  0     0
  6 19  1  1     0
  7  8  2  0     0
  7 12  1  6     0
  8  9  1  6     0
  8 20  1  1     0
  9 10  2  0     0
  9 21  1  0     0
 10 11  1  0     0
 10 22  1  6     0
 11 12  2  0     0
 11 15  1  6     0
 12 14  1  0     0
 13 23  1  1     0
 13 24  1  0     0
 13 25  1  0     0
 14 26  1  1     0
 14 27  1  0     0
 14 28  1  6     0
 15 29  1  0     0
 15 30  1  0     0
 15 31  1  6     0
M  END

[Execution by Interface]

Open Dexmedetomidin_R1.mol file by CONFLEX Interface. Interface R1

Select [CONFLEX] in Calculation menu, and click Detail Settings in the calculation setting dialog displayed. A detail setting dialog will be displayed. Basic Settings

Select [UV/Vis/CD Spectrum] in the pull-down menu of [Calculation Type:] in [General Settings] dialog on the detail setting dialog. General Settings UV/Vis/CD

Next, we set parameters for the CD/UV spectrum calculation by [UV/Vis/CD Spectrum] dialog.
Select [Specify...] in [SCF Iterations:] pull-down menu, and input 50. The maximum number of SCF iterations becomes 50.
Set [Occupied Orbital:] and [UnOccupied Orbital:] to 10, respectively. These set the number of occupied orbitals (Nomo) and unoccupied orbitals (Numo) used for one-electron excited CI calculations. UV/Vis/CD Settings

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 Dexmedetomidin_R1.ini file.

Dexmedetomidin_R1.ini file

MMFF94s CDUV SCF_ITER=50 CIS=(10,10)
  • [MMFF94S] means to use MMFF94s force field.
  • [CDUV] means to perform CD/UV spectrum calculation.
  • [SCF_ITER=50] means to set the maximum number of SCF iterations to 50.
  • [CIS=(10,10)] means to set the number of occupied orbitals (Nomo) and unoccupied orbitals (Numo) used for one-electron excited CI calculations to 10, respectively.

Store the two files of Dexmedetomidin_R1.mol and Dexmedetomidin_R1.ini in an one folder, and execute below command. The calculation will start. 

C:\CONFLEX\bin\flex9a_win_x64.exe   -par   C:\CONFLEX\par   Dexmedetomidin_R1enter

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

Calculation results

Results of the CD/UV spectrum calculation are shown at the end of Dexmedetomidin_R1.bso file.

 !---------------------------------------------------------------------------------------------------------------------!
 ! CURVE PLOTTING                                                                                                      !
 !      SCALING FACTOR:  1.00000                                                                                       !
 !---------------------------------------------------------------------------------------------------------------------!

    WAVELENGTH(NM) WAVENUMBER(1/CM)        UV(STR)        UV(VEL)        CD(VEL)
       1000.000          10000.0           0.00000        0.00000        0.00000
        980.392          10200.0           0.00000        0.00000        0.00000
        961.538          10400.0           0.00000        0.00000        0.00000
        943.396          10600.0           0.00000        0.00000        0.00000
        925.926          10800.0           0.00000        0.00000        0.00000
        909.091          11000.0           0.00000        0.00000        0.00000
        892.857          11200.0           0.00000        0.00000        0.00000
        877.193          11400.0           0.00000        0.00000        0.00000
        862.069          11600.0           0.00000        0.00000        0.00000
        847.458          11800.0           0.00000        0.00000        0.00000
......

The graph made by this data is shown below. The results of R2-R6 are also shown. CDUV Fig.1