Hi, and thanks for tips!
The calculations are performed without the entropy contributions yes. The
point was however to get a hint wether ligand binding to each of the two
proteins strengthens or weakens the protein-protein interaction. Thus, the
numbers in it self are not that interesting. I was more hoping that the
relative change could be interpreted to aid in this question.
It seems like an infinite cut-off value is common in MMPBSA calculations.
I'm doing this on a protein ~3000 residues. Thus the GB calculations with
infinite cut off are quite heavy. Would I be in trouble if I reduced the
cut-off, to around 12Å?
Kind regards,
Lars Skjaerven
On Thu, Oct 14, 2010 at 3:06 PM, case <case.biomaps.rutgers.edu> wrote:
> On Thu, Oct 14, 2010, Lars Skjærven wrote:
>
> > I'm attempting to measure the binding free-energy of a protein-protein
> > complex. Ligand binding to each of the two protein subunits are assumed
> to
> > weaken the binding energy between them.
> >
> > Thus, I performed 6 MD simulations of the complex with the two ligands,
> and
> > 6 MD simulations without the ligands. All simulations are 50 ns long.
> MMPBSA
> > was then used on each of the simulations to measure the binding free
> energy
> > in the two cases. 500 frames from each of the simulations were used in
> the
> > MMPBSA calculation.
>
> All your results seem quite reasonable. What is called "protein" and
> "ligand"
> is arbitrary, and your identification seems fine. It's also very good to
> run
> multiple simulations. What you are seeing looks to me like "natural"
> fluctuations in estimates of protein-protein binding energies, although the
> values are all very negative....are you leaving out the entropy
> contributions?
>
> The "case 2" numbers do have bigger fluctuations: you could look for
> structural differences in the individual simulations that might explain
> some
> of this. A good thing to do would be to pool all the snapshots (say for
> "case
> 2"), then cluster them. If important clusters have structures from each of
> the six simulations, that would be good. If not, you would have evidence
> that
> individual simulations were getting trapped in some region of configuration
> space.
>
> Using MMPBSA for protein-protein interactions is a challenge; if you
> haven't
> done so, please check out this paper:
>
> %A H. Gohlke
> %A D.A. Case
> %T Converging Free Energy Estimates: MM-PB(GB)SA Studies on the
> Protein-Protein Complex Ras-Raf
> %J J. Comput. Chem.
> %V 25
> %P 238-250
> %D 2004
>
> ....good luck....dac
>
>
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Received on Fri Oct 15 2010 - 10:30:04 PDT
