Hi Dipesh,
In this case, I would probably divide the system as following:
### Protein-Ligand System
Protein
Ligand
4 Na+ ions (or other cations)
X waters
### Pure Water System
X waters
### Protein System
Protein
4 Na+ ions (or other cations)
X Waters
### Ligand System
Ligand
X Waters
... where "X" is the same number for all systems and sufficiently solvates
your largest system.
It is usually possible to run a simulation without without neutralizing the
net charge, however it is not recommended. Especially if your goal is to
precisely compute potential energy terms, I would aim to neutralize all
your systems.
Also, keep in mind that even with simulations of several microseconds you
may not get your statistical uncertainty under 1-5 kcal/mol due to the size
of your system. A lot of things can contribute to this, including
conformational flexibility and slow sampling.
Good luck,
--Niel
On Mon, Jun 6, 2016 at 6:36 PM, Budhathoki, Dipesh <
budhdipe.pharmacy.isu.edu> wrote:
> 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>
>> > _______________________________________________
>> > 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
>>
>
>
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Mon Jun 06 2016 - 19:00:04 PDT
