CONFLEX Tutorials

Solvation free energy calculation

[Definition of solvation free energy]

Solvation free energy (ΔGsol) is defined as the difference in free energy of a molecule between gas and solvent phases. Therefore, to calculate the ΔGsol, we need to perform free energy calculations of the molecule based on vibrational analysis in both pahses.

Solv. Eq.1

If we assume that the vibrational contributions to the free energy are the same in the gas and solvent phases, the solvation free energy can be approximated as the difference in total energies obtained from geometry optimizations under each condition.

Solv. Eq.2

On the other hand, if we assume that the structures optimized in the gas and solvent phases are identical, the solvation free energy can be expressed as

Solv. Eq.3

CONFLEX accounts for solvent effects using the GB/SA model. For an explanation of the GB/SA model, please refer to [Calculation including solvent effects].

[Neutral glycine trimer]

This section explains how to calculate the solvation free energy using the 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 from Interface]

Open the gly3.mol file using CONFLEX Interface.

Interface Gly3

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

Next, select [GBSA] from the pull-down menu of [Solvent Effect] in [Force Field] dialog of the detailed settings dialog. Check [Solvent Energy:] check box, and select [Free Energy] from the pull-down menu.

Solvation Free Energy

The options [Free Energy], [Optimization], and [Single Point] in the [Solvation Energy:] pull-down menu correspond to the three levels of approximation (equations) for calculating solvation free energy described above.

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 gly3.ini file.

gly3.ini file

MMFF94s GBSA_ANALYZER=FREE

[GBSA_ANALYZER=FREE] indicates that the solvation free energy is calculated by performing free energy calculations based on vibrational analyses in both the gas and solvent phases.
[GBSA_ANALYZER=] keyword has three options: [FREE], [OPTIMZ], and [SINGLE], which correspond to the three levels of approximation (equations) for calculating solvation free energy described above.
[MMFF94S] means to use MMFF94s force field.

Store the gly3.mol and gly3.ini files in a single folder, and execute the following command to start the calculation.

C:\CONFLEX\bin\conflex-10a.exe   -par   C:\CONFLEX\par   gly3enter

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

Calculation results

The results of the solvation free energy calculation are output at the end of the bso file, as shown below. The first line shows the solvation free energy calculated as the difference in total energy, while the second line shows it as the difference in free energy.

Solvation free energy values for the glycine trimer (gly3.bso)

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

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