On Tue, 2014-09-16 at 17:05 +0300, Thomas Evangelidis wrote:
> Greetings,
>
> I want to run MMPBSA.py script using 3 different trajectories (complex,
> receptor, ligand). The difference between the receptor and the complex
> trajectories was that the receptor had an aspartate protonated which was
> unprotonated in the complex. This is perfectly fine in reality, but when it
> attempted to use MMPBSA.py the program complained.
This is actually not fine (at least not according to the details you've
written here). The MM/PBSA thermodynamic cycle does not accommodate
"chemical" changes (i.e., changes in covalent bonds). There is an extra
process of deprotonation and proton desolvation that is not accounted
for. So you would need to add on a thermodynamic cycle similar to the
kind used for pKa calculations and constant pH simulations.
> So I modified the
> receptor trajectory and topology by removing the extra proton from the ASP
> side-chain. However, I still get a residue mismatch error that may be cause
> by the modification I introduced. Do you believe this is the case? If yes,
> is there any work around to fix it?
MMPBSA.py takes steps to catch errors that break the assumptions of
MM/PBSA analyses (like what you are doing here). [1] Simply stripping
the extra proton will not work -- MMPBSA.py also checks that the residue
sequences are the same in the bound and unbound states (ASH != ASP) and
it checks that the atoms have the same charges in the bound and unbound
states... which they won't if all you did was strip out a hydrogen atom
using cpptraj.
You can use MMPBSA.py to process each trajectory independently and then
combine them yourself as legs of the applicable thermodynamic cycle for
your process.
HTH,
Jason
[1] It catches what it can, but can't catch everything. Just because
MMPBSA.py lets it happen doesn't mean it's "right" from a theoretical
point of view.
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
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Received on Tue Sep 16 2014 - 09:30:03 PDT
