[gmx-users] Discrepancy between Free Energy Perturbation using Gromos96 and OPLS
David
spoel at xray.bmc.uu.se
Wed Oct 12 22:45:52 CEST 2005
On Wed, 2005-10-12 at 22:18 +0200, Erik Lindahl wrote:
> Hi,
>
> A bug indeed. Fixed in both branches of CVS, and will be in a 3.3.1
> update in your near future.
>
> In the meantime, you can download an updated src/kernel/toppush.c from
>
> ftp://ftp.gromacs.org/pub/tmp/toppush.c
>
It's probably good to note that this is a bug in grompp rather than
mdrun and that it can be prevented (using manual labor) by writing the
Ryckaert-Bellemans parameters twice for each dihedral (such that A and B
state are identical).
>
> Cheers,
>
> Erik
>
>
> On Oct 12, 2005, at 11:21 AM, Erik Lindahl wrote:
>
> > Hi Sandeep,
> >
> > This could indeed be a bug. Please enter a report at http://
> > bugzilla.gromacs.org and include the appropriate files to reproduce
> > it as attachments.
> >
> > We'll probably have a look at it anyway, but it's going to be
> > longer if we need to construct a system to reproduce it first :-)
> >
> > Cheers,
> >
> > Erik
> >
> > On Oct 12, 2005, at 6:01 AM, Sandeep Somani wrote:
> >
> >
> >> Hi All
> >>
> >> I have a clue on the origin of this discrepancy. Looks like a bug
> >> in FEP
> >> code.
> >> Would like to get comments from the developers.
> >>
> >> The system I am working with is a 153 residue protein with a buried
> >> (isolated from solvent) water molecule. I am trying to find the free
> >> energy of binding of this buried water by perturbing the non-bonded
> >> interaction of the *single water molecule*.
> >>
> >> The deltaG values using different ff and gmx3.3beta are
> >>
> >> 1. OPLS ff for protein : ~ -330 kJ/mol
> >> 2. Gromos96 (ffG43a1.itp) : ~ -37 kJ/mol
> >>
> >> Clearly OPLS is incorrect.
> >>
> >> Using -sepdgdl option of mdrun in gmx3.3beta to get the components of
> >> dG/dl,
> >> a sample entry in the log file at lambda=0.5 looks like
> >>
> >> GROMOS
> >> ======
> >> Step 1000: non-bonded V and dVdl for node 0:
> >> VdW and Coulomb SR particle-p. V -3.34460e+05 dVdl 8.61080e+01
> >> RF exclusion correction V -1.01159e+04 dVdl 5.09968e-02
> >> Step 1000: bonded V and dVdl for node 0:
> >> G96Angle #2306 V 2.50156e+03 dVdl 0.00000e+00
> >> Proper Dih. # 857 V 1.30637e+03 dVdl 0.00000e+00
> >> Improper Dih. # 743 V 7.88975e+02 dVdl 0.00000e+00
> >> LJ-14 + Coulomb-14 #2561 dVdl 0.00000e+00
> >> ------
> >> OPLS
> >> ====
> >> Step 1000: non-bonded V and dVdl for node 0:
> >> VdW and Coulomb SR particle-p. V -3.42520e+05 dVdl 1.15979e+02
> >> RF exclusion correction V -1.55339e+04 dVdl 7.03910e-02
> >> Step 1000: bonded V and dVdl for node 0:
> >> Angle #4465 V 4.88804e+03 dVdl 0.00000e+00
> >> Proper Dih. # 467 V 2.79401e+02 dVdl 0.00000e+00
> >> Ryckaert-Bell. #5037 V 1.80946e+03 dVdl *-3.39702e+02*
> >> LJ-14 + Coulomb-14 #6445 dVdl 0.00000e+00
> >> --------
> >>
> >> The numbers are reasonable for Gromos.
> >> But in OPLS there is a big and non-zero "Ryckaert-Bell." term even
> >> though there are no dihedrals
> >> in the perturbed atoms. Whats the origin of this ? And how can i
> >> get rid
> >> of it ?
> >> Relevent portions of the OPLS topology file are attached.
> >>
> >> also, in the log file what do the numbers starting with # mean
> >> (#4465, #
> >> 467 etc) ?
> >>
> >> With Regards
> >> Sandeep
> >>
> >> ---
> >> Research Associate
> >> Computational Biology Group
> >> Bioinformatics Institute
> >> Singapore
> >>
> >> http://www.bii.a-star.edu.sg/~ssomani
> >>
> >>
> >>
> >>
> >>
> >>
> >>
> >>
> >>> -----Original Message-----
> >>> From: gmx-users-bounces at gromacs.org
> >>> [mailto:gmx-users-bounces at gromacs.org] On Behalf Of Sandeep Somani
> >>> Sent: Tuesday, October 04, 2005 5:57 PM
> >>> To: 'Discussion list for GROMACS users'
> >>> Subject: RE: [gmx-users] Discrepancy between Free Energy
> >>> PerturbationusingGromos96 and OPLS
> >>>
> >>>
> >>> Adding to that, as per David's suggestion, I installed
> >>> gmx3.3_rc3 and ran the same simulation again.
> >>>
> >>> The values are still similar i.e. ~ -30kJ/mol for Gromos96
> >>> and < -300kJ/mol for OPLS.
> >>>
> >>> I tried again with PME too .. still the OPLS values are much
> >>> lower than Gromos.
> >>>
> >>> am quite clueless now ! ill be happy to provide the input
> >>> files if anyone wants to probe further ..
> >>>
> >>> Regards
> >>> Sandeep
> >>>
> >>>
> >>>
> >>>
> >>>
> >>>
> >>>> -----Original Message-----
> >>>> From: gmx-users-bounces at gromacs.org
> >>>> [mailto:gmx-users-bounces at gromacs.org] On Behalf Of Maik Goette
> >>>> Sent: Tuesday, October 04, 2005 5:41 PM
> >>>> To: Discussion list for GROMACS users
> >>>> Subject: Re: [gmx-users] Discrepancy between Free Energy
> >>>> Perturbation usingGromos96 and OPLS
> >>>>
> >>>>
> >>>> Hi David
> >>>>
> >>>> Could you be a bit more precise?
> >>>> Is this difference due to a problem of united
> >>>>
> >>>>
> >>> atoms/reaction field or
> >>>
> >>>
> >>>> all atoms/reaction field. For I also use FEP with all atoms
> >>>> (amber99-port) and reaction field, I could use some info. :)
> >>>>
> >>>> Regards
> >>>>
> >>>> Maik Goette, Dipl. Biol.
> >>>> Max Planck Institute for Biophysical Chemistry
> >>>> Theoretical & computational biophysics department
> >>>> Am Fassberg 11
> >>>> 37077 Goettingen
> >>>> Germany
> >>>> Tel. : ++49 551 201 2310
> >>>> Fax : ++49 551 201 2302
> >>>> Email : mgoette[at]mpi-bpc.mpg.de
> >>>> mgoette2[at]gwdg.de
> >>>> WWW : http://www.mpibpc.gwdg.de/groups/grubmueller/
> >>>>
> >>>>
> >>>> David wrote:
> >>>>
> >>>>
> >>>>> On Sat, 2005-10-01 at 13:11 +0800, Sandeep Somani wrote:
> >>>>>
> >>>>>
> >>>>>
> >>>>>> hi all
> >>>>>>
> >>>>>> I did a Slow Growth (dummy -> real) based FEP of a small
> >>>>>>
> >>>>>>
> >>>> ligand bound
> >>>>
> >>>>
> >>>>>> to a protein using Gromos and OPLS ff. Description of
> >>>>>>
> >>>>>>
> >>>> ligand in both
> >>>>
> >>>>
> >>>>>> cases is identical.
> >>>>>>
> >>>>>> Free energy change from the Gromos simulation is
> >>>>>>
> >>>>>>
> >>> reasonable but the
> >>>
> >>>
> >>>>>> number from OPLS is an order of magnitude more negative.
> >>>>>>
> >>>>>> All parameters (reaction field electrostatics, constraints in
> >>>>>> topology, delta-lambda etc) other than the ff are
> >>>>>>
> >>>>>>
> >>>> identical. Am using
> >>>>
> >>>>
> >>>>>> gmx3.2.1.
> >>>>>>
> >>>>>> Has anyone encountered this before ? what could be the
> >>>>>>
> >>>>>>
> >>>> origin of this
> >>>>
> >>>>
> >>>>>> discrepancy ?
> >>>>>>
> >>>>>>
> >>>>>
> >>>>> It could be due to the all-atom/united atom difference in
> >>>>>
> >>>>>
> >>>> combination
> >>>>
> >>>>
> >>>>> with the reaction field. Berk has recently implemented an
> >>>>>
> >>>>>
> >>> exclusion
> >>>
> >>>
> >>>>> correction for reaction fields that could be important
> >>>>>
> >>>>>
> >>>> here. You could
> >>>>
> >>>>
> >>>>> retry it with 3.3beta to see whether there is a difference.
> >>>>>
> >>>>>
> >>>>>
> >>>>>
> >>>>>
> >>>>>> Thanks and Regards
> >>>>>> Sandeep
> >>>>>>
> >>>>>> ---
> >>>>>> Research Associate
> >>>>>> Computational Biology Group
> >>>>>> Bioinformatics Institute
> >>>>>> Singapore
> >>>>>>
> >>>>>> http://web.bii.a-star.edu.sg/~ssomani/
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>> _______________________________________________
> >>>>>> gmx-users mailing list
> >>>>>> gmx-users at gromacs.org
> >>>>>> http://www.gromacs.org/mailman/listinfo/gmx-users
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> >>>>>>
> >>>>>>
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> >>>>
> >>>
> >>>
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> >>>
> >>> <opls_prot.top>
> >>>
> >> _______________________________________________
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> >
> > -----------------------------------------------------------
> > Erik Lindahl <lindahl at sbc.su.se>
> > Assistant Professor, Stockholm Bioinformatics Center
> > Stockholm University, SE 106 91 Stockholm
> > Phone: +46 8 5537 8564 Fax: +46 8 5537 8214
> >
> >
> >
> >
> > _______________________________________________
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> >
> >
>
> -----------------------------------------------------------
> Erik Lindahl <lindahl at sbc.su.se>
> Assistant Professor, Stockholm Bioinformatics Center
> Stockholm University, SE 106 91 Stockholm
> Phone: +46 8 5537 8564 Fax: +46 8 5537 8214
>
>
>
>
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--
David.
________________________________________________________________________
David van der Spoel, PhD, Assoc. Prof., Molecular Biophysics group,
Dept. of Cell and Molecular Biology, Uppsala University.
Husargatan 3, Box 596, 75124 Uppsala, Sweden
phone: 46 18 471 4205 fax: 46 18 511 755
spoel at xray.bmc.uu.se spoel at gromacs.org http://xray.bmc.uu.se/~spoel
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