6*monomer(aq) -----------> hexamer(aq)
^ dGf(aq) ^
| |
| dGsol1 | dGSol2
| |
6*monomer(vac) ------------> hexamer(vac)
dGf(vac)
So it seems like you want dGf(aq).
You can calculate this using 2 simulations, one for the hexamer and one for
the monomer.
dGf(aq)=dGf(vac)+dGSol2-dGSol1
since the ligand and receptor are the same in your case, the thermodynamic
cycle is simpler than in most mmpbsa applications.
You can get the needed dG values by hand by running mmpbsa 'stability'
calculations over the hexamer and single monomer trajectories and taking
appropriate sums / differences of the results.
You will likely need to get series results not just final averages so that
you can make sure the energy converges since this is essentially lile using
separate trajectories for receptor ligand and complex, so nonbonded terms
will not cancel as in single trajectory case.
On Sat, Mar 30, 2019, 1:44 AM Abhilash J <md.scfbio.gmail.com> wrote:
> Hi,
>
> I am not an expert with MMGB/PBSA but I working sometime back on a
> single protein binding to multiple ligands simultaneously.
> Your case seems slightly different. But the following might help.
> You can define complex.prmtop drug.prmtop etc... using residue numbers
> in ante-MMPBSA.py.
> Look for -s and -m options in ante-MMPBSA.py part of AMBER manual.
>
> For example:
> python $AMBERHOME/ante-MMPBSA.py -p complex_wat.prmtop -c complex.prmtop
> -r protein.prmtop -l drg.top -s '!(:1-589)' -m '!(:586)'
> Here, residues 1-589 form the complex.
> and residue 586 is the ligand. In Your case it might be residues 400-450
> as your ligand is a protein in itself.
> You can define your complex, receptor and ligand based on residue
> numbers in your topology.
> I am bit confused with your statement " I want to define one monomer as
> receptor and rest of the five monomers as five ligands". I presume it is
> other way round. Or i got this wrong.
> Still, I hope it helps.
> All the best.
>
>
>
> Abhilash
>
>
>
>
> On Sat, Mar 30, 2019 at 11:16 AM Prabir Khatua <prabir07chem.gmail.com>
> wrote:
>
> > Hi Elvis,
> >
> > I do not understand what want to mean by all the ligands bound to
> receptor
> > simultaneously. I want to calculate binding free energy of a hexamer.
> > However, I have simulated trajectory of the hexamer (complex in my case)
> > only. Thus, I want to define one monomer as receptor and rest of the five
> > monomers as five ligands considering the fact that the monomers bind one
> > after another to form hexamer. Thus, the binding free energy that I am
> > looking for should be
> >
> > Del G = G_hexa-G_mon1-G_mon2-G_mon3-G_mon4-G_mon5 -G_mon5
> >
> > However, I did not find a way to define multiple ligands and hence, I am
> > not getting the right value of binding free energy as far as the process
> of
> > hexamer formation is concerned. I hope I have made the problem clear to
> > you. Please let me know if I answered your query and help me to sort
> > out the problem.
> >
> > Thank you so much,
> >
> > Prabir
> >
> > On Fri, Mar 29, 2019 at 11:38 PM Elvis Martis <elvis.martis.bcp.edu.in>
> > wrote:
> >
> > > HI,
> > > Are all the ligands bound to the receptor simultaneously?
> > >
> > >
> > > Best Regards
> > >
> > > Elvis Martis
> > >
> > >
> > >
> > > ________________________________
> > > From: Prabir Khatua <prabir07chem.gmail.com>
> > > Sent: 30 March 2019 02:44
> > > To: AMBER Mailing List
> > > Subject: [AMBER] MMPBSA
> > >
> > > Hello Amber Users,
> > >
> > > I want to calculate binding free energy of a complex having five
> > identical
> > > ligands. I really do not know how to define the ligand prmtop file in
> > > MMPBSA.py.
> > >
> > > I tried something like
> > >
> > > mpirun -np 8 $AMBERHOME/bin/MMPBSA.py.MPI -O -i mmgbsa-1.in -o
> > > SAA_2_hexa_104_S1_mmgbsa.dat -do SAA_2_hexa_104_S1_mmgbsa-decomp.dat
> -cp
> > > com.prmtop -rp rec.prmtop -lp lig1.prmtop lig2.prmtop lig3.prmtop
> > > lig4.prmtop lig5.prmtop -y SAA_2_hexa_104_S1.crd
> > >
> > > However, it is not working. Can anyone please suggest me how to use
> > > multiple ligands in a single MMPBSA calculation? Any suggestion would
> be
> > > appreciated.
> > >
> > > Thanks,
> > >
> > > Prabir
> > >
> > > --
> > >
> > > *Prabir Khatua*
> > > *Postdoctoral Research Associate*
> > > *Department of Chemistry & Biochemistry*
> > > *University of Oklahoma*
> > > *Norman, Oklahoma 73019*
> > > *U. S. A.*
> > > _______________________________________________
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> > > AMBER.ambermd.org
> > > http://lists.ambermd.org/mailman/listinfo/amber
> > > _______________________________________________
> > > AMBER mailing list
> > > AMBER.ambermd.org
> > > http://lists.ambermd.org/mailman/listinfo/amber
> > >
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> >
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Received on Sat Mar 30 2019 - 13:00:02 PDT
