Great (a25, assuming all up to date).
Pass along your input file (copy and paste here and don’t forget to cc
the amber list email too pls).
What force field, water model, ion force fields and numbers (tleap
inputs would be great)?
There’s a nonzero chance you did everything as well as can be done.
After sending your inputs and execution steps, look at the raw
trajectories in search of water and or ions that have nestled between
your protein and DNA. If there’s a water mediated protein-DNA
interaction, MMPBSA probably won’t be able to recapitulate the
energetic of that (think an acidic aa pointed at the backbone of DNA,
mediated by a water or maybe cation).
Bon chance
Kevin
On May 11, 2026, at 10:26 AM, Surabhi Singh 24933024
<surabhi_s.bt.iitr.ac.in> wrote:
Hey Kevin,
I'm using Amber25 .
Thanks,
Surabhi
On Mon, May 11, 2026 at 7:34 PM Kevin Hauser <[1]84hauser.gmail.com>
wrote:
Hey there!
What version of amber are you using?
Best,
Kevin
> On May 11, 2026, at 9:04 AM, Surabhi Singh 24933024 via AMBER
<[2]amber.ambermd.org> wrote:
>
> Hello Amber Team,
>
> I am currently working on *protein–DNA complexes *and have
completed energy
> minimization followed by 250 ns production MD simulations.
>
> I am now performing MMPBSA calculations for multiple complexes
involving
> protein bound to standard DNA as well as mutated DNA sequences. In
my
> setup, I considered the protein as the receptor and DNA as the
ligand.
>
> However, I am observing positive ΔG binding values for these
systems, which
> is confusing because, for other complexes analyzed using the same
workflow
> and parameters, I obtained negative ΔG values as expected.
>
> I would like to understand the possible reasons behind these
positive
> binding free energies. Could this be related to the highly charged
nature
> of protein–DNA systems and electrostatic contributions affecting
the MMPBSA
> calculations? Or is there something specific that should be
considered
> while applying MMPBSA to protein–DNA complexes?
>
> I would greatly appreciate any suggestions or insights regarding
this issue.
>
>
> Thanks,
> Surabhi Singh
> Ph.D. Computational Biology
> Biosciences and Bioengineering, IIT Roorkee
> _______________________________________________
> AMBER mailing list
> [3]AMBER.ambermd.org
> [4]http://lists.ambermd.org/mailman/listinfo/amber
References
1. mailto:84hauser.gmail.com
2. mailto:
amber.ambermd.org
3. mailto:AMBER.ambermd.org
4.
http://lists.ambermd.org/mailman/listinfo/amber
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Received on Mon May 11 2026 - 08:00:02 PDT
