Jason,
Many thanks for the prompt and very helpful reply.
I’m interested in option 4: lB -- sA.sB and lA -- sA.lB.sB
I had a quick look at ante-MMPBSA.py help. As I’ve never used the script before I’d be grateful for one additional clarification.
Given the above option and that ligand lA is residue 126 of my current topology:
1. Is the following script correct?
-p lA.sA.lB.sB_solv.prmtop -c lA.sA.lB.sB.prmtop -r sA.lB.sB.prmtop -l lA.prmtop -s :126 -n :126 --radii=mbondi2
Once again, thanks very much for your kind help
Regards
George
On 26Feb, 2015, at 1:11 PM, Jason Swails <jason.swails.gmail.com> wrote:
> On Thu, 2015-02-26 at 12:46 -0300, George Tzotzos wrote:
>> I’m dealing with a homo-dimer (A and B subunits) in complex with two
>> identical ligands.
>>
>> In MMGBSA calculations, I considered as complex the dimer
>> (A/ligandA-B/ligandB), as receptor (sub-unit A/ligandA) and as ligand
>> (sub-unit B/ligandB). The calculation resulted in the expected output.
>>
>> I’d like now to determine deltaG binding of ligandA and ligandB. I
>> have the parameter files of both ligands. I’m a bit stuck on how to do
>> this without re-running MD simulations.
>
> So you have 4 components: ligand A (lA), subunit A (sA), ligand B (lB),
> subunit B (sB). You got the binding energy between lA.sA -- lB.sB. What
> binding energies are you looking for now? I can think of 5 "popular"
> possibilities -- the one you pick depends on what you want to learn:
>
> lA -- sA.lB.sB and lB -- lA.sA.sB ?
> lA -- sA.sB and lB -- sA.sB ?
> lA -- sA.sB and lB -- lA.sA.sB ?
> lB -- sA.sB and lA -- sA.lB.sB ?
> lB -- sB and lA -- sA?
>
> or some combination of those? You can either run the simulations of
> those systems necessary, or you can generate them from the simulation of
> lA.sA.lB.sB that you already did using cpptraj. For example, let's
> consider the first two scenarios above:
>
> lA -- sA.lB.sB : you need the original lA.sA.lB.sB topology, the lA
> topology, and the sA.lB.sB topology. You can generate the latter two
> (ligand and receptor) using ante-MMPBSA.py giving it a set of masks. The
> second part of that line is the same idea, just lB instead of lA.
>
> lA -- sA.sB : Your 'complex' topology is now lA.sA.sB, so you need to
> use cpptraj to strip lB from the trajectory and print out a compatible
> prmtop file along with the corresponding trajectory (you might as well
> also strip water and ions so MMPBSA.py doesn't need to do that step).
> Then you need to create sA.sB and lA topologies (you can get those from
> ante-MMPBSA.py, as well).
>
> That gives you the basic template for how to extract trajectories for
> any of the systems above you want to define as the 'complex'... just
> note that the more you strip away, the more perturbed your system is and
> the less representative the generated trajectory will be of the 'true'
> trajectory. At some point (who knows what point), cancellation of
> errors won't be enough. But these seem to me to be outstanding,
> unanswered questions in the field.
>
> HTH,
> Jason
>
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
>
>
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Received on Thu Feb 26 2015 - 09:30:03 PST
