Dear Neil,
Thank you for your clear explanation about the procedure.My protein is a
bit larger (258 residues, 1950 atoms) which contains NAD as cofactor.
The net charge of -4 in the protein, whereas ligand is neutral.Do the
system need to be neutral before minimization?
Best regards,
Dipesh
On Mon, Jun 6, 2016 at 1:58 PM, Niel Henriksen <shireham.gmail.com> wrote:
> Hi Dipesh,
>
> Unfortunately Leap does not have an automatic method to add a precise
> number of water molecules to your system. If you only have a few
> simulations to run, the easiest approach is to add just a bit too much
> water, and then delete the extra. This is what you see done in the
> tutorial.
>
> For your particular case, you need to first decide how much water your
> protein-ligand complex needs for a successful simulation. Usually a 12
> angstrom solvent buffer is a good place to start, so you might try
> something like 'solvatebox ProtLig TIP3PBOX 12.0 iso' . Leap will then
> tell you how many water molecules it added.
>
> Suppose it added 7000 water molecules. For the simplest approach to the
> binding enthalpy calculation, the other three simulations need to have an
> identical number of waters. So the protein alone would have 7000, the
> ligand alone would have 7000, and then you would need a pure water
> simulation with 7000. To do this, just experiment with changing the buffer
> value number until you get slightly above 7000; then remove as necessary.
> That way, the waters in ProteinLigand + PureWater = ProteinAlone +
> LigandAlone.
>
> It can get a little more complicated if there are net charges on your
> protein and or ligand. Also, for large systems, the statistical
> uncertainty can increase to the point of being completely uninformative.
> There are some ways to minimize the uncertainty, like only computing
> relative enthalpy difference. If you need specific help, let me know a
> little more about your system and I can help you out.
>
> If you plan to run a lot of simulations, I have a script which might be
> able to automate the addition of waters for you.
>
> --Niel
>
>
> On Mon, Jun 6, 2016 at 11:06 AM, Budhathoki, Dipesh <
> budhdipe.pharmacy.isu.edu> wrote:
>
> > Hi amber,
> > I am trying to calculate the binding enthalpy of protein-ligand system
> > using explicit solvent.When I followed the Amber tutorial 21, they have
> > mentioned that the water molecules should balance between the bound set
> of
> > simulations(complex and pure water) and unbound set of simulatuions(host
> > and guest).How can I add equal number of water molecules between the
> bound
> > and unbound set of simulations?What could be the proper box size for the
> > leap preparatory files.In amber tutorial 21, they have used following box
> > sizes for bound and unbound states.
> > solvatebox purewater TIP3PBOX 16.50 iso
> > solvatebox b2 TIP3PBOX 13.16 iso
> > solvatebox CB7 TIP3PBOX 10.18 iso
> > solvatebox b2-CB7 TIP3PBOX 9.91 iso
> >
> > They have also removed water above 1500 to maintain equal number of water
> > molecules between bound and unbound set of simulations.
> >
> > Sincerely,
> > Dipesh <http://lists.ambermd.org/mailman/listinfo/amber>
> > _______________________________________________
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> > http://lists.ambermd.org/mailman/listinfo/amber
> >
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Received on Mon Jun 06 2016 - 19:00:03 PDT
