Re: [AMBER] working with mmpbsa with protein and three ligands in same complex

From: Sadaf Rani <>
Date: Wed, 20 Jan 2021 11:42:20 +0500

Dear Dac
Thank you very much for your reply.
I tried one of the state as below:-
            "A" "B"
Protein+cofactor1+cofactor2 ligand
both of the cofactors are the same but bind at the different binding sites.
Is it the correct way?

I am getting the error with ligand prmtop as mentioned below:- -O -i -o FINAL_RESULTS_MMPBSA.dat -sp complex.prmtop
-cp complexdry.prmtop -rp protein_cofactordry.prmtop -lp G6P_n.prmtop -y
Loading and checking parameter files for compatibility...
cpptraj found! Using /home/rcms/Downloads/Amber/amber20/bin/cpptraj
mmpbsa_py_energy found! Using
Preparing trajectories for simulation...
2000 frames were processed by cpptraj for use in calculation.

Running calculations on normal system...

Beginning GB calculations with
  calculating complex contribution...
  calculating receptor contribution...
  calculating ligand contribution...
  File "/home/rcms/Downloads/Amber/amber20/bin/", line 100, in
line 218, in run_mmpbsa, self.stdout)
line 82, in run, stdout=stdout, stderr=stderr)
line 475, in run
    raise CalcError('%s failed with prmtop %s!' % (self.program,
CalcError: /home/rcms/Downloads/Amber/amber20/bin/cpptraj failed with
prmtop G6P_n.prmtop!
Exiting. All files have been retained.

Could you please suggest to me where I am doing mistake?
Thanks in advance.


On Sun, 17 Jan 2021 at 20:17, David A Case <> wrote:

> On Sun, Jan 17, 2021, Sadaf Rani wrote:
> >I have a query and need your suggestions, please. I want to calculate
> >ligand binding affinities of a protein-ligand complex in which I have 1
> >ligand and two cofacors in the same complex. How should I calculate
> binding
> >affinities of all with protein using mmpbsa? Do I need to built separate
> >complexes for all of the three ligands (ligand plus cofactors)?
> Don't be confused by the terms "protein", "ligand" and "complex". MMPBSA
> doesn't know any chemistry, it effectively always treats a two-component
> system, A + B -> C, where A, B and C can be anything you want.
> To describe the binding of three components, you could do some combination
> of the following calculations, depending on what information you wish to
> obtain; (in this table, "C" would alway be the combination of "A" and "B"):
> "A" "B"
> ----------------------------------------------
> 1. protein ligand
> 2. protein+ligand cofactor1
> 3. protein+ligand+cofactor1 cofactor2
> 4. protein+cofactor1 ligand
> ....etc...etc. The order of the calculations doesn't matter, at least
> in principle. And you probably don't need all the steps. With a protein
> plus three binders, there are *many* possible states, depending on whether
> each binder has its own pocket (and so can only bind in one place), and
> whether the two cofactors are the same or different. If each binder can
> only bind in its "own" pocket, you would have
> nothing bound 1 state
> 1 item bound 3 states
> 2 items bound 3 states
> 3 items bound 1 state
> But is is very rare that you would want to simulate all of them.
> ...hope this helps....dac
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Received on Tue Jan 19 2021 - 23:00:02 PST
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