CONFLEX Tutorials

CD/UV spectrum analysis

Dexmedetomidine is a medetomidine activator (D-form), featuring an imidazole skeleton, and acts as a highly potent and selective central α2 adrenaline receptor agonist. By stimulating central α2 receptors, it inhibits sympathetic nerve signal transmission and produces a sedative effect. Additionally, this molecule exhibits the simplest form of optical activity.
This section explains how to perform CD/UV spectrum calculations 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 from Interface]

Open the Dexmedetomidin.mol file using CONFLEX Interface.

Interface Dexmedetomidin

Select [CONFLEX] from the Calculation menu, and then click Detail Settings in the calculation setting dialog that appears. A detailed settings dialog will be displayed.

Basic Settings

Select [Conformation Search] from the [Calculation Type:] pull-down menu in [General Settings] dialog of the detailed settings dialog. General Settings

Edit the value of [Search Limit:] to 50.0 in [Conformation Search] dialog of the detailed settings dialog.
When completing the calculation settings, click Edit & Submit. Conformation Search

Add [PRECHK] to the dialog that appears, and then click Submit to start the calculation. Edit and Submit

[Execution from command line]

The calculation settings are defined by specifying 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 a single folder, and execute the following command to start the calculation. 

C:\CONFLEX\bin\conflex-10a.exe   -par   C:\CONFLEX\par   Dexmedetomidinenter

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

Calculation results

We can obtaine six 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 are performed for the conformers. The structure data for conformers R1–R6 are stored in the Dexmedetomidine.sdf in MDL MOL file format. Here, we extract the structure data of the R1 conformer from Dexmedetomidine.sdf and save it 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 from Interface]

Open Dexmedetomidin_R1.mol file using CONFLEX Interface. Interface R1

Select [CONFLEX] from the Calculation menu, and then click Detail Settings in the calculation setting dialog that appears. A detailed settings dialog will be displayed. Basic Settings

Select [UV/Vis/CD Spectrum] from the pull-down menu of [Calculation Type:] in [General Settings] dialog of the detailed settings dialog. General Settings UV/Vis/CD

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

After completing the calculation settings, click Submit to start the calculation.

[Execution from command line]

The calculation settings are defined by specifying 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 a single folder, and execute the following command to start the calculation. 

C:\CONFLEX\bin\conflex-10a.exe   -par   C:\CONFLEX\par   Dexmedetomidin_R1enter

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

Calculation results

The results of 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 generated from this data is shown below, along with the results for conformers R2–R6. CDUV Fig.1