Just for info, I've been working with a trimer to which three ligands
bind, and I can confirm that MM/PBSA and MM/GBSA analysis works as
expected with this kind of setup. In the longer term, you'll probably
want to run the calculations against both of the ligands so that you get
a 'two for one' benefit from your trajectiories.
Is it possible that you have defined the receptor/ligand boundaries
slightly incorrectly, so that one or two ligand residues are in the
receptor, or vice versa? I have found this easy to do and it does give
rise to large delta delta Gs.
All the best
William
On 24/10/2016 19:03, Jag Silwal wrote:
> Dear all,
>
> I ran a simulation for protein complexes which includes four chains as
> shown below. Protein "C" is a dimer and protein A binds to protein C and I
> am interested to run MM-PBSA to estimate binding free energy between
> protein A and protein C in its dimeric form.
> Fo MM-PBSA, I created a separate PDB file for A and another PDB file with
> the rest of the proteins (C-C dimer +another A). Then for the MMPBSA
> command I treated A as the ligand protein and C-C dimer + A as receptor
> protein. I ran with the following script:
>
>
> &general
> |startframe=4501, endframe=5550, interval=5,
> |verbose=2, keep_files=2, strip_mask=':WAT,CL',
> |/
> |&gb
> |igb=8, saltcon=0.150,
> |/
> |&pb
> |inp=1, radiopt=0, istrng=0.15, fillratio=4.0
> |/
>
>
> When the run was done I checked the Delta delta G and it came to be about
> 1000 kcal/mol which I think is way too high for the interface.
> Previously, I have separately ran and analyzed the Delta delta G without
> the dimer where there is only one A and one C the Delta delta G was -60
> kcal/mol.
>
> So I am sure I am not either setting these different PDBs right or may be I
> am missing something important while setting up for MM-PB/GBSA analysis.
> How do I approach this problem?
>
> Any insight would be really appreciated.
>
>
>
> [image: Inline image 2]
>
>
>
>
>
> Sincerely,
>
> Jag
> Graduate Student,
> Michigan State University
> Department of Chemistry
>
>
>
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Received on Tue Oct 25 2016 - 03:30:02 PDT
