On Mon, Oct 12, 2015 at 12:14 PM, anu chandra <anu80125.gmail.com> wrote:
> Dear Amber users,
>
> I am trying to calculate the binding free energy change for the protein
> complex I am working with. The system contains protein A-ligand complexed
> with protein B and protein C. I also have another system of unliganded
> protein A complexed with protein B and protein C. Now, I am trying to
> calculate the binding free energy change in protein A with B and C. I have
> few queries here regarding setting up the complex for the MMPBSA.py
> calculation.
>
> In all calculation, I will be considering Protein A ( with or without
> ligand) as receptor.
>
> 1. If I want to calculate the free energy between protein A with protein B,
> do I need to consider protein C in the complex and receptor? i.e.,
>
> Complex : protein A+protein B+protein C
> Receptor : protein A+protein C
> Ligand : protein B
>
>
> 2. Do I need to consider ligand bound to the protein A as a part of
> receptor while using protein A as the receptor?
>
The answer depends on the question you are asking and what you want to
learn.
The situation you just described will give you the binding free energy of
the Protein A-Protein C complex binding with Protein B. This will be quite
different than Protein A and Protein C forming a complex in absence of
Protein B. Which one do you want? What are you trying to compute or
learn? That will dictate how you have to define your different systems.
The same thing applies to having the ligand bound to protein A. Do you
want to know the binding free energy in the presence of the ligand, or
not? That will dictate how you should define your systems.
One thing I'll point out here is that single-trajectory MM/PBSA is really
bad at capturing allostery (for obvious reasons). When asking these kinds
of questions, I think allostery often plays a big role in distinguishing
between A-C and A+B-C interactions. So if you suspect allosteric
contributions to binding, you will likely need to use multiple trajectories
at the very least. Most importantly, however, is to define very
specifically the problem you are trying to solve.
HTH,
Jason
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
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Received on Mon Oct 12 2015 - 10:00:03 PDT
