[gmx-users] Fwd: FW: PME settings in free energy calculations

Mark Abraham mark.j.abraham at gmail.com
Tue Feb 9 09:20:29 CET 2016


Hi,

On Fri, Feb 5, 2016 at 1:32 PM Dries Van Rompaey <dries.vanrompaey at gmail.com>
wrote:

> Hi,
>
> The corresponding mdp output section is:
>
> ; OPTIONS FOR ELECTROSTATICS AND VDW
> ; Method for doing electrostatics
> coulombtype              = PME
> coulomb-modifier         = Potential-shift-Verlet
> rcoulomb-switch          = 0
> rcoulomb                 = 1.0
> ; Relative dielectric constant for the medium and the reaction field
> epsilon-r                = 1
> epsilon-rf               = 0
> ; Method for doing Van der Waals
> vdwtype                  = cutoff
> vdw-modifier             = Potential-switch
> ; cut-off lengths
> rvdw-switch              = 0.9
> rvdw                     = 1.0
> ; Apply long range dispersion corrections for Energy and Pressure
> DispCorr                 = EnerPres
> ; Extension of the potential lookup tables beyond the cut-off
> table-extension          = 1
> ; Separate tables between energy group pairs
> energygrp-table          =
> ; Spacing for the PME/PPPM FFT grid
> fourierspacing           = 0.08
> ; FFT grid size, when a value is 0 fourierspacing will be used
> fourier-nx               = 0
> fourier-ny               = 0
> fourier-nz               = 0
> ; EWALD/PME/PPPM parameters
> pme_order                = 6
> ewald_rtol               = 1e-06
> ewald-rtol-lj            = 0.001
> lj-pme-comb-rule         = Geometric
> ewald-geometry           = 3d
> epsilon_surface          = 0


That all seems reasonable.


> I evaluated the energy with:
>
> Verlet - settings above (with standard verlet-buffer-tolerance)
> @ s0 legend "Coulomb-14"
> @ s1 legend "Coulomb (SR)"
> @ s2 legend "Coul. recip."
>     0.000000  -2221.295898  -546205.250000  9271.518555
> Total -     539155.0273
>
> Verlet - settings above - with verlet-buffer-tolerance -1
>     0.000000  -2221.295898  -546205.250000  9271.516602
> Total   -539155.029296
>

That kind of agreement is expected, but perhaps might agree exactly if you
were following
http://www.gromacs.org/Documentation/How-tos/Single-Point_Energy

Group - settings above
> @ s0 legend "Coulomb-14"
> @ s1 legend "Coulomb (SR)"
> @ s2 legend "Coul. recip."
>     0.000000  -2221.296387  -487993.593750  -48931.437500
> Total -539146.3276
>

The difference in those components is expected - in PME you have to avoid
counting contributions in the long-range part from pairs that are excluded
e.g. from the bonded topology. The two schemes handle this in different
places. Their sum should match (within the limits of floating-point
arithmetic), and a relative error under 1e-5 for summing a few million
numbers is acceptable for judging the equivalence of the implementations.

Verlet - 3 nm cutoffs, 2.9 vdwswitch, coulomb-modifier none
> @ s0 legend "Coulomb-14"
> @ s1 legend "Coulomb (SR)"
>     0.000000  -2221.295898  -774817.875000
> Total -777039.1709
>
>
> Group - 3 nm cutoffs, 2.9 vdwswitch, coulomb-modifier none
> @ s0 legend "Coulomb-14"
> @ s1 legend "Coulomb (SR)"
>     0.000000  -2221.296387  -553398.125000
> Total -555619.4214
>

That ought to agree much better, but It's hard to speculate on where the
problem lies without seeing log files. Please upload some to a file sharing
service and post the links here (list doesn't take attachments)

Mark


> Thanks,
>
> Dries
>
> On 4 February 2016 at 14:48, Michael Shirts <mrshirts at gmail.com> wrote:
>
> > Also, can you be more precise about the inconsistency in the outputs
> > you are seeing (with numerical output from GROMACS and analysis code).
> >
> > On Thu, Feb 4, 2016 at 6:17 AM, Michael Shirts <mrshirts at gmail.com>
> wrote:
> > > Hi, Dries-
> > >
> > > Can you print out what the corresponding section of mdout.mdp look
> like?
> > >
> > > Have you  tried using the cutoffs above with group cutoffs, and seen
> > > what the difference is?
> > >
> > > On Thu, Feb 4, 2016 at 4:59 AM, Dries Van Rompaey
> > > <dries.vanrompaey at gmail.com> wrote:
> > >> Hi,
> > >>
> > >> I'm using PME with the default Potential-Shift-Verlet modifier. If I'm
> > >> interpreting the manual and comments on the mailinglist correctly, the
> > >> settings for rcoulomb-switch shouldn't affect this and PME-switching
> > >> shouldn't be necessary (although there seems to have been some
> > discussion
> > >> about this, https://gerrit.gromacs.org/#/c/2220/). Has a consensus
> been
> > >> reached elsewhere?
> > >>
> > >> Current nonbonded settings in my .mdp files are:
> > >> ; Electrostatics
> > >> coulombtype              = PME
> > >> rcoulomb                    = 1.0
> > >>
> > >> ; van der Waals
> > >> vdwtype                    = cutoff
> > >> vdw-modifier            = Potential-switch
> > >> rvdw-switch              = 0.9
> > >> rvdw                         = 1.0
> > >>
> > >> ; Apply long range dispersion corrections for Energy and Pressure
> > >> DispCorr                  = EnerPres
> > >>
> > >> ; Spacing for the PME/PPPM FFT grid
> > >> fourierspacing           = 0.08
> > >>
> > >> ; EWALD/PME/PPPM parameters
> > >> pme_order                = 6
> > >> ewald_rtol                 = 1e-06
> > >> epsilon_surface        = 0
> > >>
> > >> Thanks in advance,
> > >>
> > >> Dries
> > >>
> > >> On 4 February 2016 at 00:56, Michael Shirts <mrshirts at gmail.com>
> wrote:
> > >>
> > >>> Hi, Dries-
> > >>>
> > >>> Questions like this are probably best answered on the gmx-users list.
> > >>> I can't say too much for the Verlet scheme -- I know that it was
> > >>> relatively recently adapted for free energies, and there may be some
> > >>> combinations of settings that could give unanticipated results.
> > >>>
> > >>> Pretty much all of our experience about nonbonded calculations and
> > >>> free energies is collected in the following paper:
> > >>> http://pubs.acs.org/doi/abs/10.1021/ct4005068. We used the group
> > >>> cutoff scheme since that was the only one that was supported in
> > >>> GROMACS at the time.
> > >>>
> > >>> Since you haven't sent any files, it's hard to tell what is actually
> > >>> going on. The one thing that has a tendency to happen with the more
> > >>> recent update schemes is if you set a potential modifier that is a
> > >>> switch, but don't set the distance the switch starts at, then it is
> > >>> automatically set to zero.  Check the mdout.mdp to see if this is
> > >>> happening.
> > >>>
> > >>> > From: Van Rompaey Dries <Dries.VanRompaey at uantwerpen.be>
> > >>> Date: Wednesday, February 3, 2016 at 12:34 PM
> > >>> To: Michael Shirts <michael.shirts at colorado.edu>
> > >>> Subject: PME settings in free energy calculations
> > >>>
> > >>> Dear prof. Shirts,
> > >>>
> > >>> I'm currently trying to figure out the PME settings for a relative
> > >>> free binding energy simulation I'm working on. I took the parameters
> > >>> from Matteo Aldeghi's
> > >>> paper(
> > >>>
> >
> http://pubs.rsc.org/en/content/articlelanding/2015/sc/c5sc02678d#!divAbstract
> > >>> )
> > >>> as a starting point (adapted for the Verlet scheme by scaling the
> > >>> fourierspacing to 0.08 and setting coulomb = rvdw = 1.0). I then
> tried
> > >>> to verify these settings by comparing a single point energy
> > >>> calculation with these settings and one with very long coulomb
> cutoffs
> > >>> as recommended on alchemistry.org.
> > >>>
> > >>> Unfortunately, I can't seem to get this quite right. I'm getting
> > >>> differences in the hundreds of kj/mol, leading me to suspect I'm
> doing
> > >>> something wrong. I'm calculating the energy values by extracting
> > >>> CoulombSR and Coul-recip from the energy.xvg files. I've tried
> > >>> calculating the energy with coulomb cutoffs at 3 nm and 10 nm, but
> > >>> agreement with the PME results remains rather poor. David Mobley
> > >>> mentioned you performed extensive research on this topic, and I'm
> > >>> hoping you could point me in the right direction.
> > >>>
> > >>> Thanks in advance,
> > >>>
> > >>> Dries
> > >>>
> > >>>
> > >>>
> > >>> ~~~~~~~~~~~~~~~~
> > >>> Michael Shirts
> > >>> Associate Professor
> > >>> michael.shirts at colorado.edu
> > >>> Phone: (303) 735-7860
> > >>> Office: JSCBB D317
> > >>> Department of Chemical and Biological Engineering
> > >>> University of Colorado Boulder
> > >>> --
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