George,
Your first two results results look like it'd well within the natural range
of fluctuations, although your third run seems to be a little bit further
than what I'd expect, given how close 1 and 2 are. It's enough to warrant
looking more closely at the structure to see if there's anything else going
on, if nothing else; someone with more expertise than me may be able to
give you more insight.
I'd also note that MMPBSA shouldn't be the only tool you're using if you're
trying to see if dimerization is more favored- protein-protein interactions
with MMPBSA at best might only provide an idea of if a ligand is promoting
the dimers, and I'd be careful about making conclusions based solely on
delta G values.
Best,
Kenneth
On Wed, May 20, 2015 at 2:37 PM, George Tzotzos <gtzotzos.me.com> wrote:
> Maybe the question was silly or I failed to communicate it correctly
>
> What I’m trying to establish is whether ligand binding favours or
> disfavours binding of two chains of a homodimer.
>
> Assuming two consecutive MD simulations involving:
>
> 1. A homodimer (chainA-chainB)
> 2. the same homodimer plus ligand X (chainA-X-chainB-X)
>
> and treating chainA of the homodimer as the receptor and chainB as ligand
> would it be legitimate to assume that dimerisation is favoured if deltaG
> (chainA-X-chainB-X) < deltaG (chainA-chainB) ?
>
> The second question is whether stripping the ligand from (2) would lead to
> perturbations such that a comparison of deltaGs (chainA-chainB) from the
> two trajectories is meaningless.
>
>
> > On 20 May 2015, at 14:09, George Tzotzos <gtzotzos.me.com> wrote:
> >
> > I’ve run 3 consecutive MD simulations of 100ns each. A summary of
> delta-G total obtained by MMGBSA is given below.
> >
> > 1. homodimer. One of the chains treated as receptor the other as ligand.
> delta-G total -29kcal/mol
> > 2. homodimer + 2 ligands (a & b). Used ante-mmpbsa.py to strip ligands
> (a & b) and generate topologies for chainA( to be treated as receptor) and
> chainB(to be treated as ligand). delta-G total -24kcal/mol
> > 2. homodimer + 2 ligands (c & d). Repeated method used in 2. above.
> delta-G total -40 kcal/mol
> >
> > Clarification: single trajectories were used.
> >
> > Is such variation in delta-G total for binding of chainA to chainB to be
> expected? Is this due to perturbations upon ligand binding. Similar
> variation in delta-G was observed for binding of ligands to the dimer and
> the same ligands to the monomer (DIFFERENT MD runs)
> >
> > My objective is to determine whether the ligands stabilise or not dimer
> formation. Is the approach described above suitable for the purpose?
> >
> > Thank you in advance for any comments/suggestions
> >
> > Regards
> >
> > George
> >
> >
> >
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
>
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
Ask yourselves, all of you, what power would hell have if those imprisoned
here could not dream of heaven?
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Wed May 20 2015 - 12:30:02 PDT
