Dear Niel,
Thanks a lot for all these information
Best regards,
Dipesh
On Mon, Jun 6, 2016 at 7:56 PM, Niel Henriksen <shireham.gmail.com> wrote:
> 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 - 21:00:02 PDT
