Hi George,
On Wed, Jan 5, 2011 at 7:28 AM, George Tzotzos <gtzotzos.me.com> wrote:
> Jason many thanks for this. Answers my questions.
>
> Going through the output files and the Amber11 manual, I noticed that I had
> NOT set PBradii to mbondi2.
>
> How critical is this?
>
This method was parameterized against the mbondi2 PBRadii, so it should be
set. That being said, the difference between mbondi2 and the default
(mbondi) radii sets are minimal. I think only a couple atoms have different
radii, and they don't differ extensively.
>
> Can I prepare de novo my prmtop files setting PBradii to mbondi2 and then
> re-run MMPBSA.py using the new topology files on the trajectories generated
> from the topology files without mbondi2 set?
>
The script will certainly let you. Did you generate the MD trajectory with
implicit solvent? If so, the *proper* ensemble may not have been sampled
properly. I have no idea what kind of effect this may have. Maybe it's a
major effect, maybe it's minor. The safe bet would be to remake the
trajectory from the proper radii. However, if you used explicit solvent,
then the radii weren't used at all and it's a moot point.
Good luck,
Jason
All the best
>
> George
>
>
> On Jan 4, 2011, at 10:32 PM, Jason Swails wrote:
>
> > Hi George,
> >
> > These are two different GB models. While both follow the OBC equation
> (see
> > the Onufriev, Bashford, Case paper describing them, cited in the Amber
> > manual), the alpha, beta, and gamma parameters are different between the
> two
> > of them, so you can't expect the results to be the same.
> >
> > Try using the same GB model and you should get the same results.
> >
> > Good luck!
> > Jason
> >
> > On Tue, Jan 4, 2011 at 12:35 PM, George Tzotzos <gtzotzos.me.com> wrote:
> >
> >> Hi Jason,
> >>
> >> Many thanks for the comprehensive replies.
> >>
> >> With regard to your question if the difference is between the serial and
> >> parallel implementations of MMPBSA.py the answer is NO. Both runs were
> made
> >> with the parallel implementation.
> >>
> >> The only difference is that in the per-residue decomposition igb was set
> to
> >> 5 (default) whereas in the calculation of total energy igb was set to 2.
> >>
> >> Please see the namelists below.
> >>
> >> George
> >> ==========================
> >>
> >> Per-residue GB and PB decomposition
> >> &general
> >> endframe=50, verbose=1,
> >> /
> >> &gb
> >> igb=5, saltcon=0.100,
> >> /
> >> &pb
> >> istrng=0.100,
> >> /
> >> &decomp
> >> idecomp=1,
> >> dec_verbose=1,
> >> /
> >> ===========================
> >>
> >> Input file for running PB and GB
> >> &general
> >> endframe=50, verbose=1,
> >> # entropy=1,
> >> /
> >> &gb
> >> igb=2, saltcon=0.100
> >> /
> >> &pb
> >> istrng=0.100,
> >> /
> >> ============================
> >> On Jan 4, 2011, at 7:59 PM, Jason Swails wrote:
> >>
> >>> Hello,
> >>>
> >>> My comments are below.
> >>>
> >>> On Tue, Jan 4, 2011 at 3:41 AM, George Tzotzos <gtzotzos.me.com>
> wrote:
> >>>
> >>>> Happy New Year to all,
> >>>>
> >>>> I've been running MMPBSA.py.MPI to determine Delta G for a
> >> protein-ligand.
> >>>> I've also run the program to determine per residue decomposition of
> >>>> entropy.
> >>>>
> >>>
> >>>> The same input files have been used in both cases. The the Delta G
> >> results
> >>>> obtained from Generalized Born differ by ~ 2kcal/mol
> >>>>
> >>>
> >>> Is this the difference between parallel and serial or the difference
> >> between
> >>> decomp turned on and decomp turned off? Also, what individual terms
> >> differ
> >>> between the two calculations? It could be that the algorithm used to
> >>> compute the surface area between the two methods is slightly different.
> >>>
> >>>
> >>>>
> >>>> For example,
> >>>>
> >>>> Differences (Complex - Receptor - Ligand):
> >>>>
> >>>> DELTA G binding = -46.6213 +/- 3.1112
> >>>> 0.1663 (given by per-residue entropy
> >>>> decomposition)
> >>>> DELTA G binding = -44.2279 +/- 2.7619
> >>>> 0.1476 (without per-residue entropy
> >>>> decomposition)
> >>>>
> >>>> The same discrepancy of ~2kcal/mol has been observed using the same
> >> ligand
> >>>> with two (2) other receptors.
> >>>>
> >>>> The Poisson Boltzmann calculations with and without per residue
> >>>> decomposition gave identical values
> >>>>
> >>>
> >>> As far as I know, the surface area is non-decomposable for PBSA, so
> this
> >> is
> >>> not really a factor. Hence, you get similar/identical results.
> >>>
> >>>
> >>>>
> >>>> Differences (Complex - Receptor - Ligand):
> >>>>
> >>>> DELTA G binding = -34.0898 +/- 3.1112
> >>>> 0.1663
> >>>>
> >>>> My specific questions are the following:
> >>>>
> >>>> 1. Is there an explanation for this discrepancy in the case of
> >> Generalized
> >>>> Born while this discrepancy is not observed in the Poisson Boltzmann
> >>>> calculations?
> >>>>
> >>>> 2. The Delta Gs given by the two methods are different by ~10
> kcal/mol.
> >>>> That strikes me as being too much of a difference.
> >>>>
> >>>
> >>> This is not unusual, and reflects the method's shortcomings when
> >> calculating
> >>> absolute binding free energies. A better comparison to make would be
> the
> >>> DELTA Delta G between different receptors with the same ligand or
> >> different
> >>> ligands with the same receptor.
> >>>
> >>>
> >>>>
> >>>> 3. Is temperature (say 300K) factored in the ENTROPY calculations?
> >>>>
> >>>
> >>> Yes. There should be a comment in the output file saying exactly that.
> >> On
> >>> the tutorial website, the last line of text in the output file says
> >>>
> >>> NOTE: All entropy results have units kcal/mol. (Temperature has already
> >> been
> >>> multiplied in as 300. K)
> >>>
> >>>
> >>>> 4. Can one assume that the enthalpy for the six translational and
> >>>> rotational degrees of freedom is 6*(1/2)*RT=1.8 kcal/mol at 300K?
> >>>>
> >>>
> >>> No. The entropy is calculated from statistical mechanical equations
> >> using
> >>> the partition function assuming that the translational, rotational, and
> >>> vibrational parts of the Hamiltonian are separable. This introduces a
> >>> mass-dependence of the translational entropy.
> >>>
> >>> Note that this email was begun in response to your first message, so my
> >>> later email will address future questions.
> >>>
> >>> Good luck!
> >>> Jason
> >>>
> >>>
> >>>> Thanks in advance and best regards
> >>>>
> >>>> George
> >>>>
> >>>> _______________________________________________
> >>>> AMBER mailing list
> >>>> AMBER.ambermd.org
> >>>> http://lists.ambermd.org/mailman/listinfo/amber
> >>>>
> >>>
> >>>
> >>>
> >>> --
> >>> Jason M. Swails
> >>> Quantum Theory Project,
> >>> University of Florida
> >>> Ph.D. Graduate Student
> >>> 352-392-4032
> >>> _______________________________________________
> >>> AMBER mailing list
> >>> AMBER.ambermd.org
> >>> http://lists.ambermd.org/mailman/listinfo/amber
> >>
> >>
> >> _______________________________________________
> >> AMBER mailing list
> >> AMBER.ambermd.org
> >> http://lists.ambermd.org/mailman/listinfo/amber
> >>
> >
> >
> >
> > --
> > Jason M. Swails
> > Quantum Theory Project,
> > University of Florida
> > Ph.D. Graduate Student
> > 352-392-4032
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
Jason M. Swails
Quantum Theory Project,
University of Florida
Ph.D. Graduate Student
352-392-4032
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Received on Wed Jan 05 2011 - 08:30:04 PST
