Hi,
On Tue, Dec 25, 2018 at 8:05 AM Farial Tavakoli
<faryal.tavakoli.gmail.com> wrote:
> I am trying to calculate the binding free energy of 2 complexes including a
> protein in wild type and mutant state in complex with a ligand which has 2
> phosphotyrosines, using MMPBSA. There are some charged residues in the
> binding pocket of both proteins: including:
> mutant receptor: asp, arg, asp, arg, lys, lys
> wild type receptor: asp, arg, asp, lys, lys
> peptide has to phosphotyrosines and a histidine (HID)
> I expected the delta total in both complexes are the same or close to each
> other , but they are so different. The delta total in mutant complex is -12
> kcal/mol , whereas the delta total in wild type mutant is -30 kcal/mol.
> The experimental binding energy was calculated and it was -10 kcal/mol.
> I dont know why the calculated binding free energy using mmpbsa in both
> proteins are not the same.
Why do you expect the binding free energy to be close? Is the -10
kcal/mol experimental number for the WT, mutant, or is it the change
in binding FE from the WT to mutant? Reproducing absolute binding free
energies with MMPBSA/GBSA is notoriously difficult; you're better off
trying to reproduce DDG.
> I need to know whether the solute dielectric constant definition for
> binding pocket or whole the protein?
> Would you please advice me which number I should put for the internal
> dielectric?
The internal dielectric applies to anything that is "solute". The
exact value to use is a matter of some debate in the literature, but
it is typical to see values ranging from 1-4. You may want to
experiment with different values, but you should first ensure that
your MMPBSA/GBSA results are converged to eliminate that as a
potential source of error.
-Dan
>
> Best regard
> Farial
>
> my input file is :
> &general
> startframe=1, endframe=1000, interval=10,
> verbose=2, keep_files=0,
> /
> &pb
> istrng=0.15, fillratio=4.0, indi=4, exdi=80,
> /
> and this is mmpbsa command:
> mpirun -np 16 MMPBSA.py.MPI -O -i mp.in -o final.dat -sp
> complex_solvated.top -cp complex.top -rp receptor.top -lp ligand.top -y
> .mdcrd
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Received on Fri Dec 28 2018 - 06:30:02 PST
