Re: [AMBER] mmpbsa number of atoms issues

From: Ayesha Fatima <>
Date: Sun, 15 Sep 2013 12:42:35 +0700

Thanks Jason,
I shall try the suggestions and perhaps share my experience.
thanks again

On Sun, Sep 15, 2013 at 11:05 AM, Jason Swails <>wrote:

> On Sat, Sep 14, 2013 at 6:44 AM, Ayesha Fatima <
> >wrote:
> > Dear All,
> > I am trying to calculate the binding energy for my complex. I run into a
> > familiar issue of incorrect atom numbers between prmtop and crd files. I
> > have searched the tutorials and also the mailing list but i cannot find a
> > specific solution. I am sure it is easy but i am unable to put my finger
> on
> > it.
> >
> > The complex i simulated has water molecules in the binding site which i
> > want to retain. when i want to generate the prmtop files, i am confused.
> > the order of the atoms in the complex is protein-ligand-water in binding
> > site. I prepared the prmtop files for the complex for mmpbsa by stripping
> > the added water besides the water in the binding site. The prmtop file
> > prepared for the prtotein alone also has the water in the binding site.
> The
> > prmtop file of the ligand is of the ligand only, nothing extra.
> >
> >
> > Q1 Where should i get the value for the RSTART AND RSTOP AND the LSTART
> and
> > LSTOP? Which pdb file to consider. is it the one which is used in the
> > simulation? This is by far the most confusing part since this the file to
> > generate the snapshots because when i want to write the RSTART and
> RSTOP, i
> > am not sure what should be written.
> >
> I'm not very familiar with the Perl script, but you can check to see if you
> can specify multiple values of RSTART and RSTOP. If not, I don't see any
> easy way of using to compute your binding free energy (it may
> be
> worth studying the manual and examples in this case).
> > Q2 How do i account for the water molecules in the binding site? Should
> > they be removed also when preparing the prmtop files for the mmpbsa?
> >
> They are typically removed, but if the waters play a crucial, structural
> role then implicit solvent models are unlikely to treat them properly
> (except perhaps 3D-RISM). Continuum models treat all solvent-occupied
> regions as bulk solvents, in general (the GB and PB approaches, that is).
> If a water molecule behaves very differently in your protein than it does
> in bulk, your answers may be very dependent on that water molecule being
> present.
> You can always test your ideas by computing binding free energies of
> different systems (with and without explicit waters).
> >
> > Q3 Could there be an issue with the order of the complex atoms? Should it
> > be protein-ligand-water in binding site or protein-water in binding site-
> > ligand?
> >
> It's best not to think of your system as a 3-part system. You have 2 parts
> -- a receptor and a ligand. Whether you consider the water as part of the
> receptor or ligand depends on what you want to calculate and what you are
> trying to learn. In either case, tleap will likely create the topology
> file with the water at the end (but otherwise the residue sequence will be
> the same as it is in the original PDB file).
> > Q4 if i change the order of atoms, should i run the md again? by right i
> > should, but is there a way around the problem?
> >
> Have you tried I know that it can handle such systems without
> having to jump through many hoops. (And changing the order of atoms in a
> topology file is no easy task -- especially when tleap tends to put waters
> at the very end).
> Finally, you can also compute MM/PBSA free energies 'by hand' -- that is,
> don't use either or and run the necessary energy
> calculations manually. If you have never done this before, it may be a
> useful exercise -- it should yield insight into the theoretical basis of
> the method as well as what the scripts are automating at each step (which
> should in turn help you learn how to use the scripts more easily and
> effectively).
> HTH,
> Jason
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
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Received on Sat Sep 14 2013 - 23:00:02 PDT
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