Thanks!
For the first question, I guess I am looking for some empirical criterion
such as overall RMSD.
For your second point, the complex is an X-ray solved structure (not in
vivo). Actually, we are quite skeptical about that calcium-binding site
because there is no formal charge involved.
Xue
On Fri, Sep 17, 2010 at 4:19 PM, Bill Miller III <brmilleriii.gmail.com>wrote:
> 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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> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
>
>
>
> --
> 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 - 14:00:03 PDT
