Binding Energy Calculation

In this section we will calculate the electrostatic binding energy for the FKBP12-butanone system in two different conformations, one with the ligand distal from the protein (comp_dist.pqr) and one with it bound (comp_bound.pqr). This time we will use the psize.py script provided in the apbs distribution at $APBSHOME/tools/manip/psize.py and included in your directory to calculate the suggested grid dimensions.

        

psize.py comp_bound.pqr

The psize.py script uses a default 0.5 Angstrom grid resolution. This can be changed with the option --SCALE 0.75 . All other options are listed when the script is run with no arguments. The suggested grid dimensions have been used for cglen, fglen, and dime in fkbp_binding.in and fkbp_binding2.in. Execute the two APBS calculations with the following:

apbs fkbp_binding_bound.in > fkbp_binding_bound.out apbs fkbp_binding_dist.in > fkbp_binding_dist.out

Notice that we use automatic focusing this time (mg-auto) to generate the finer data from the coarser calculations performed in the visualization example.

Important: In any electrostatic energy calculation, care needs to be taken to remove self-interaction terms. In this example, we remove the self-interaction energies via a series of calculations which use exactly the same grid spacings, lengths, and centers. Since all atoms in the complex are present in the apo protein and ligand, the self-interaction terms are effectively removed.

Question: Why are the electrostatic binding energies so similar?!? Why isn't the bound form more favorable??

Keep in mind that we have not yet accounted for apolar contributions. These terms, which usally scale with the solvent-accessible surface area (SASA), favor binding.

Using another program from the APBS distribution ($APBSHOME/tools/manip/acc) and included in your directory acc, we can determine how much solvent-accessible surface area is lost when the complex is formed. This is done for for you in the calc_nonpolar.sh script where the first argument is the name of the complex, dist/bound.

./calc_nonpolar.sh dist ./calc_nonpolar.sh bound

☻ Even a conservative value of the apolar energy surface tension ,which usually ranges between 0.105 to 210 kJ/A2, reveals that this buried surface area provides stabilization to the complex. ☻