CONFLEX Tutorials

Solvation free energy calculation

[Definition of solvation free energy]

Solvation free energy (ΔGsol) expresses as a difference in free energy of a molecule in a gas phase and in a solvent. Therefore, in order to calculate the ΔGsol, we have to perform free energy calculations of the molecule based on a vibrational analyses in the gas phase and in the solvent.

Solv. Eq.1

When assuming that the contributions of vibrations to the free energy are equal in the gas phase and in the solvent, the solvation free energy is a difference of the total energies obtained by structure optimizations under each condition.

Solv. Eq.2

On the other hand, when assuming that the structures optimized in the gas phase and in the solvent match, the solvation free energy can be expressed as

Solv. Eq.3

CONFLEX considers the solvent effects by using GB/SA model. About explanation of GB/SA model, please refer to [Calculation with solvent effects].

[Neutral glycine trimer]

This section explains how to perform a solvation free energy calculation using neutral glycine trimer as an example.

Structural formula of neutral glycine trimer

Glycine Trimer

Structure data of neutral glycine trimer (gly3.mol)

gly3.mol


 24 23  0  0  0  0  0  0  0  0  0    0
   -2.5597   -2.2710    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5552   -1.1275    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.1846   -2.1941   -0.8898 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.1846   -2.1941    0.8898 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8628   -3.5653    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3212   -1.3741    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0265    0.2649    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2897   -3.6354   -0.8165 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2897   -3.6353    0.8164 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0071    0.4608   -0.0002 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0702    1.3535    0.0002 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7917    2.6935    0.0002 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4442    1.2877    0.8902 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4439    1.2878   -0.8895 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.0496    2.7309   -0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0193    3.9442    0.0004 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0197    3.9147    0.0006 H   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7064    5.2200    0.0003 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7020    6.3635    0.0005 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3310    5.2967   -0.8896 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3314    5.2967    0.8900 H   0  0  0  0  0  0  0  0  0  0  0  0
    0.5321    6.1170    0.0007 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1606    7.7180    0.0005 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4062    8.3117    0.0007 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0  0  0  0
  1  3  1  0  0  0  0
  1  4  1  0  0  0  0
  1  5  1  0  0  0  0
  2  6  2  0  0  0  0
  2  7  1  0  0  0  0
  5  8  1  0  0  0  0
  5  9  1  0  0  0  0
  7 10  1  0  0  0  0
  7 11  1  0  0  0  0
 11 12  1  0  0  0  0
 11 13  1  0  0  0  0
 11 14  1  0  0  0  0
 12 15  2  0  0  0  0
 12 16  1  0  0  0  0
 16 17  1  0  0  0  0
 16 18  1  0  0  0  0
 18 19  1  0  0  0  0
 18 20  1  0  0  0  0
 18 21  1  0  0  0  0
 19 22  2  0  0  0  0
 19 23  1  0  0  0  0
 23 24  1  0  0  0  0
M  END

[Execution by Interface]

Open the gly3.mol file by CONFLEX Interface.

Interface Gly3

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

Basic Settings

Next, select [GB/SA] in the pull-down menu of [Solvent Effect] in [Force Field] dialog on the detail setting dialog. Check [Solvent Energy:] check box, and select [Free Energy] in the pull-down menu.

Solvation Free Energy

[Free Energy], [Optimization], and [Single Point] in [Solvation Energy:] pull-down menu are corresponding to three approximate levels (equations) on the calculation of solvation free energy mentioned above, respectively.

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 gly3.ini file.

gly3.ini file

MMFF94s GBSA_ANALYZER=FREE

[GBSA_ANALYZER=FREE] means to obtain the solvation free energy by performing free energy calculations of the molecule based on vibrational analyses in the gas phase and in the solvent. [GBSA_ANALYZER=] keyword has three options of [FREE], [OPTIMZ], and [SINGLE]. These options are corresponding to three approximate levels (equations) on the calculation of solvation free energy mentioned above, respectively.
[MMFF94S] means to use MMFF94s force field.

Store the gly3.mol and gly3.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   gly3enter

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

Calculation results

Results of the solvation free energy calculation are outputted at the end of the bso file as shown below.
The first row shows the difference in the total energy as the solvation free energy,
and the second row shows the difference in the free energy as the solvation free energy.

Values of solvation free energy for glycine trimer (gly3.bso)

SOLVATION ENERGY (DIFF. OF TOTAL ENERGY) = -28.37934 (KCAL/MOL)

SOLVATION ENERGY (DIFF. OF  FREE ENERGY) = -32.29427 (KCAL/MOL)