See below.
-Bill
On Fri, Sep 17, 2010 at 4:08 PM, xue wang <xue.qfs.gmail.com> wrote:
> Dear Dr. Ray Luo,
>
> Thanks for your suggestion. I changed fillratio to be 4 in _is_init.f,
> is_init.f and mm_pbsa_createinput.pm. I obtained the following
> snapshot_statistics.out.
>
> I have two questions on this mm_pbsa calculation of binding free energy.
>
> 1). According to the tutorial, mm_pbsa does not calculate entropy because
> it assumes there is no significant conformational change. I am wondering
> how
> much is *significant* conformational change? In my case, there is some
> *local
> conformational change* upon the binding of *calcium ion*.
>
This assumption is really system-specific. Some systems are known to have
significant conformational changes upon binding, while others do not. If
your system is known to have a relatively significant conformational change
upon binding of calcium, it might be a good idea for you to look into
performing the entropy calculation as well. If you are simply trying to get
relative free energies of binding for several similar ligands (i.e. ions in
your case), then the entropy calculation may not even be necessary.
>
> 2). With respect to calcium, do you have an idea of the accuracy of
> mm_pbsa
> calculation.
>
I don't know how accurate MM-PBSA is regarding the binding of a single
calcium ion, but I would guess that these results are fairly inaccurate
since they give you a positive free energy of binding (GB: 55.89 kcal/mol
and PB:286.38 kcal/mol). If the complex stays together *in vivo* then you
know this answer has to be incorrect. For clarification, I am not saying
that MM-PBSA cannot do what you are asking, but it doesn't appear to have
done it given these results.
>
>
> # COMPLEX RECEPTOR LIGAND
> # ----------------------- -----------------------
> -----------------------
> # MEAN STD MEAN STD
> MEAN STD
> # ======================= =======================
> =======================
> ELE -543.97 63.58 -816.71 58.45
> 0.00 0.00
> VDW -442.25 18.44 -456.77 18.05
> 0.00 0.00
> INT 2656.05 32.63 2656.05 32.63
> 0.00 0.00
> GAS 1669.83 67.39 1382.57 62.39
> 0.00 0.00
> PBSUR 58.84 1.31 58.86 1.31
> 0.87 0.00
> PBCAL 0.00 0.00 0.00 0.00
> 0.00 0.00
> PBSOL 58.84 1.31 58.86 1.31
> 0.87 0.00
> PBELE -543.97 63.58 -816.71 58.45
> 0.00 0.00
> PBTOT 1728.67 67.35 1441.42 62.61
> 0.87 0.00
> GBSUR 58.84 1.31 58.86 1.31
> 0.87 0.00
> GB -5503.78 56.99 -4808.18 51.28
> -465.11 0.00
> GBSOL -5444.95 57.04 -4749.33 51.02
> -464.24 0.00
> GBELE -6047.75 17.48 -5624.90 17.73
> -465.11 0.00
> GBTOT -3775.11 30.04 -3366.76 30.23
> -464.24 0.00
>
> # DELTA
> # -----------------------
> # MEAN STD
> # =======================
> ELE 272.75 21.04
> VDW 14.52 3.21
> INT 0.00 0.00
> GAS 287.27 20.48
> PBSUR -0.89 0.01
> PBCAL 0.00 0.00
> PBSOL -0.89 0.01
> PBELE 272.75 21.04
> PBTOT 286.38 20.48
> GBSUR -0.89 0.01
> GB -230.49 19.33
> GBSOL -231.38 19.33
> GBELE 42.26 4.27
> GBTOT 55.89 3.31
>
>
> Thanks a lot!
>
> Regards,
>
> Xue
>
>
>
>
>
>
>
>
>
>
>
>
> On Wed, Sep 1, 2010 at 5:49 PM, Ray Luo <ray.luo.uci.edu> wrote:
>
> > For a single ion, the coordinate really doesn't matter. The energy
> > will be a constant throughput the trajectory.
> >
> > As for the failure on the single ion calculation, it's probably due to
> > the complaint in PBSA that fillratio (=2) is set to be too small if you
> > are using one of the earlier Amber distributions. Do a search on the
> > list to find out how to add "fillratio =4" in the PBSA input, which is
> > automatically generated by the perl script.
> >
> > All the best,
> > Ray
> >
> > ==========================================
> > Ray Luo, Ph.D.
> > Associate Professor in Computational
> > Biochemistry and Molecular Biophysics
> > Dept of Molecular Biology and Biochemistry
> > Dept of Biomedical Engineering
> > University of California, Irvine, CA 92697-3900
> > Email: rluo.uci.edu Phones: (949) 824-9528, 9562
> > Web: http://rayl0.bio.uci.edu/rayl/
> > ==========================================
> >
> >
> > On 9/1/2010 1:14 PM, xue wang wrote:
> > > Hello everyone! I have been trying to calculate the binding free energy
> > > between protein and calcium ion using mm_pbsa.pl. I've successfully
> got
> > > snapshot_com.crd.*, snapshot_rec.crd.* and snapshot_lig.crd.*, but
> failed
> > > when tried to calculate binding energy from these snapshots. The log
> > file
> > > indicates that this program failed when it got to snapshot_lig.crd.1.
> The
> > > following is part of log file including the failure point. I also
> noticed
> > > that the PDB file generated for ligand (calcium here) has coordinates
> > > (0.000, 0.000, 0.000) for calcium, which is not true because
> > > snapshot_lig.crd.1 gave another set of coordinates. Could anyone tell
> me
> > why
> > > this happened? Is it a particular problem for metal ligand? Thanks a
> lot!
> > >
> > >
> > > Calc contrib for ./snapshot_rec.crd.199
> > > Calc MM/GB/SAS
> > > Generate PDB
> > > Center PDB
> > > Calc PBSA
> > > Generate PQR
> > > Calc MS
> > > Calc contrib for ./snapshot_rec.crd.200
> > > Calc MM/GB/SAS
> > > Generate PDB
> > > Center PDB
> > > Calc PBSA
> > > Generate PQR
> > > Calc MS
> > > Calc contrib for ./snapshot_lig.crd.1
> > > Calc MM/GB/SAS
> > > Generate PDB
> > > Center PDB
> > > Calc PBSA
> > >
> > >
> > >
> > > Xue
> > > _______________________________________________
> > > 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
> >
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>
--
Bill Miller III
Quantum Theory Project,
University of Florida
Ph.D. Graduate Student
352-392-6715
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Received on Fri Sep 17 2010 - 13:30:05 PDT
