# [gmx-users] -inf potential with TPIC

Rafael I. Silverman y de la Vega rsilverm at ucsc.edu
Sat Jun 14 00:10:46 CEST 2014

```Hi João,
I dont think its an excessive number of unfavorable insertions. The mu
getting output with double precision are
Reading frame      40 time 1770.000   mu -6.570e+01 <mu> -7.654e+01
Reading frame      50 time 1775.000   mu -4.985e+01 <mu> -7.609e+01
Reading frame      60 time 1780.000   mu -7.010e+01 <mu> -7.571e+01
Reading frame      70 time 1785.000   mu -5.669e+01 <mu> -7.540e+01
Reading frame      80 time 1790.000   mu -4.749e+01 <mu> -7.511e+01
Reading frame      90 time 1795.000   mu -7.355e+01 <mu> -7.590e+01

to give a fairly representative sample. So, no, they arent near 100, and
are negative... And the issue seems to happen with later insertions, not
the first few... One run I just did, only the very last average mu was
-inf, (not even the mu for that frame, just the average mu after that
frame) which really seems to imply some sort of overflow problem

Reading frame     180 time 1790.000   mu -1.284e+02 <mu> -1.153e+02
Reading frame     190 time 1795.000   mu -7.920e+01 <mu>       -inf
(not the same run as above, this was run in single precision)

On Thu, Jun 12, 2014 at 7:06 AM, João M. Damas <jmdamas at itqb.unl.pt> wrote:

> Hello Rafael,
>
> High energies (energy differences) are not discarded. When summing them
> through the exponential of their negative, they contribute very little to
> the final sum (lower energies dominate the sum). Hence, they are
>
> The "-inf" value on the mu standard error output is normal because, unlike
> the -tpi output, there is no ternary operator checking if the sum of
> exponentials is equal to zero (when it is, the log of zero gives you the
> inf value).
>
> The change to the double precision not giving you the "-inf" also makes
> sense, because the sum of exponentials, which on single-precision was zero,
> can now be non-zero due to the higher number of decimal places on
> double-precision. I am guessing with double-precision you are getting very
> high positive numbers (energies) for the mu, around 1000 maybe?
>
> My interpretation is that it is hard to find a "favorable place" to insert
> the water molecule in that cavity, at least with a few frames. I am
> guessing that with more and more frames, that may change, which is natural.
>
> I hope this has helped.
>
> Cheers,
> João
>
>
>
> On Thu, Jun 12, 2014 at 10:45 AM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
> >
> >
> > On 6/11/14, 8:55 PM, Rafael I. Silverman y de la Vega wrote:
> >
> >> I mistyped amber, when I should have typed charmm, amber is totally
> >> uninvolved in  my calculations. I used the script from
> titled
> >> charmm2gromacs. The output looked fine after running it.
> >>
> >> And, I doubt its the cofactor,  just ran the insertion with double
> >> precision mdrun, it gave reasonable looking results. There seems to be
> >> some
> >> sort of issue with unreasonable interaction energies not being discarded
> >> properly.
> >>
> >>
> > It's entirely possible that there's something wrong with the tpic code;
> > you can certainly file a bug report on Redmine with input files to
> > reproduce it.
> >
> >
> > -Justin
> >
> >
> >> On Tue, Jun 10, 2014 at 3:41 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
> >>
> >>
> >>>
> >>> On 6/10/14, 6:14 PM, Rafael I. Silverman y de la Vega wrote:
> >>>
> >>>  I meant that I only changed to cofactor to gromacs chamm27 format, not
> >>>> amber format. I used charmm27 for the apoprotein as well as the
> >>>> cofactor.
> >>>>
> >>>>
> >>>>  What script did you use?  I don't understand why Amber99SB is
> involved
> >>> here, so I don't know exactly what you were doing to create the
> topology.
> >>>   It may not end up being useful information, but it's important to
> >>> establish the validity of the underlying physical model.
> >>>
> >>>
> >>> -Justin
> >>>
> >>>
> >>>  On Tue, Jun 10, 2014 at 3:09 PM, Justin Lemkul <jalemkul at vt.edu>
> wrote:
> >>>>
> >>>>
> >>>>
> >>>>> On 6/10/14, 6:04 PM, Rafael I. Silverman y de la Vega wrote:
> >>>>>
> >>>>>   you think it was the cofactor model?
> >>>>>
> >>>>>>
> >>>>>>
> >>>>>>   If you're using a CHARMM-parametrized cofactor with an Amber99SB
> >>>>>>
> >>>>> protein,
> >>>>> I'd say the simulations are wholly unreliable.  It's certainly the #1
> >>>>> likely cause for nonsensical results.  If you want to get to the root
> >>>>> of
> >>>>> the issue, you need to start with a solid foundation.
> >>>>>
> >>>>> Unless that's not what your last message meant?  When you say "only
> >>>>> changed the cofactor," that implied to me that you didn't
> consistently
> >>>>> convert everything in the system.
> >>>>>
> >>>>>
> >>>>> -Justin
> >>>>>
> >>>>>
> >>>>>   On Tue, Jun 10, 2014 at 2:23 PM, Justin Lemkul <jalemkul at vt.edu>
> >>>>> wrote:
> >>>>>
> >>>>>>
> >>>>>>
> >>>>>>
> >>>>>>  On 6/10/14, 5:01 PM, Rafael I. Silverman y de la Vega wrote:
> >>>>>>>
> >>>>>>>    wait, I only changed  the cofactor to gromacs charmm27.ff format
> >>>>>>>
> >>>>>>>
> >>>>>>>>
> >>>>>>>>    Pretty amazing that the simulation even ran with that mash-up
> of
> >>>>>>>>
> >>>>>>>>  parameters :)
> >>>>>>>
> >>>>>>> I'd say that's the most likely cause of your problems; nonsensical
> >>>>>>> physical model leads to nonsensical output.
> >>>>>>>
> >>>>>>> -Justin
> >>>>>>>
> >>>>>>>
> >>>>>>>
> >>>>>>>    On Tue, Jun 10, 2014 at 1:58 PM, Rafael I. Silverman y de la
> Vega
> >>>>>>> <
> >>>>>>>
> >>>>>>>  rsilverm at ucsc.edu> wrote:
> >>>>>>>>
> >>>>>>>>     I suppose something might be wrong with the simulations. I am
> >>>>>>>> using
> >>>>>>>>
> >>>>>>>>   gromacs 4.6.5, I am simulating a protein with a cofactor,
> someone
> >>>>>>>>
> >>>>>>>>> else
> >>>>>>>>> parametrized it, I changed from charmm to gromacs amber99sb.ff
> >>>>>>>>> format
> >>>>>>>>> with
> >>>>>>>>> a script on the gromacs website.  I did a typical em/nvt/npt
> >>>>>>>>> equilibration
> >>>>>>>>> followed by a 5 ns production run. I picked 250 frames out of the
> >>>>>>>>> trajectory, and altered them to the TPIC input format with a
> >>>>>>>>> script I
> >>>>>>>>> wrote, to insert the particle half way between two atoms that I
> >>>>>>>>> chose.
> >>>>>>>>> I
> >>>>>>>>> am
> >>>>>>>>> inserting a water molecule. When I run the actual insertion some
> of
> >>>>>>>>> the
> >>>>>>>>> frames have a reasonable looking mu, and some have -inf mu. I
> think
> >>>>>>>>> it
> >>>>>>>>> may
> >>>>>>>>> have to do with cavity size, some frames have too small of a
> >>>>>>>>> cavity,
> >>>>>>>>> so
> >>>>>>>>> the
> >>>>>>>>> interaction energy of the inserted water diverges...
> >>>>>>>>>
> >>>>>>>>>
> >>>>>>>>> On Mon, Jun 9, 2014 at 6:40 PM, Justin Lemkul <jalemkul at vt.edu>
> >>>>>>>>> wrote:
> >>>>>>>>>
> >>>>>>>>>
> >>>>>>>>>
> >>>>>>>>>   On 6/9/14, 6:41 PM, Rafael I. Silverman y de la Vega wrote:
> >>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>     Hi all, I am having a problem with -inf mu coming out of
> TPIC
> >>>>>>>>>>
> >>>>>>>>>>   calculations.
> >>>>>>>>>>
> >>>>>>>>>>> Anyone have some suggestions on how to avoid this? Tabulated
> >>>>>>>>>>> potentials?
> >>>>>>>>>>> Or
> >>>>>>>>>>> can I modify the source code to reject the absurd values that
> >>>>>>>>>>> cause
> >>>>>>>>>>> this? I
> >>>>>>>>>>> read a few old discussions on this, I didnt see much on how to
> >>>>>>>>>>> handle
> >>>>>>>>>>> this.
> >>>>>>>>>>>
> >>>>>>>>>>>
> >>>>>>>>>>>     I'd be much more concerned that something is going wrong in
> >>>>>>>>>>> the
> >>>>>>>>>>>
> >>>>>>>>>>>   simulations.  I have no experience with TPIC, but if you post
> >>>>>>>>>>> more
> >>>>>>>>>>>
> >>>>>>>>>> detailed
> >>>>>>>>>> information about what you're doing and which Gromacs version
> >>>>>>>>>> you're
> >>>>>>>>>> using,
> >>>>>>>>>> you're more likely to get some suggestions.
> >>>>>>>>>>
> >>>>>>>>>> -Justin
> >>>>>>>>>>
> >>>>>>>>>> --
> >>>>>>>>>> ==================================================
> >>>>>>>>>>
> >>>>>>>>>> Justin A. Lemkul, Ph.D.
> >>>>>>>>>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
> >>>>>>>>>>
> >>>>>>>>>> Department of Pharmaceutical Sciences
> >>>>>>>>>> School of Pharmacy
> >>>>>>>>>> Health Sciences Facility II, Room 601
> >>>>>>>>>> University of Maryland, Baltimore
> >>>>>>>>>> 20 Penn St.
> >>>>>>>>>> Baltimore, MD 21201
> >>>>>>>>>>
> >>>>>>>>>> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> >>>>>>>>>> http://mackerell.umaryland.edu/~jalemkul
> >>>>>>>>>>
> >>>>>>>>>> ==================================================
> >>>>>>>>>> --
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> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>
> >>>>>>>>>>     --
> >>>>>>>>>
> >>>>>>>>>  ==================================================
> >>>>>>>>
> >>>>>>>
> >>>>>>> Justin A. Lemkul, Ph.D.
> >>>>>>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
> >>>>>>>
> >>>>>>> Department of Pharmaceutical Sciences
> >>>>>>> School of Pharmacy
> >>>>>>> Health Sciences Facility II, Room 601
> >>>>>>> University of Maryland, Baltimore
> >>>>>>> 20 Penn St.
> >>>>>>> Baltimore, MD 21201
> >>>>>>>
> >>>>>>> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> >>>>>>> http://mackerell.umaryland.edu/~jalemkul
> >>>>>>>
> >>>>>>> ==================================================
> >>>>>>> --
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> >>>>>>>
> >>>>>>>   --
> >>>>>>>
> >>>>>> ==================================================
> >>>>>
> >>>>> Justin A. Lemkul, Ph.D.
> >>>>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
> >>>>>
> >>>>> Department of Pharmaceutical Sciences
> >>>>> School of Pharmacy
> >>>>> Health Sciences Facility II, Room 601
> >>>>> University of Maryland, Baltimore
> >>>>> 20 Penn St.
> >>>>> Baltimore, MD 21201
> >>>>>
> >>>>> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> >>>>> http://mackerell.umaryland.edu/~jalemkul
> >>>>>
> >>>>> ==================================================
> >>>>> --
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> >>>>>
> >>>>>
> >>>>>  --
> >>> ==================================================
> >>>
> >>> Justin A. Lemkul, Ph.D.
> >>> Ruth L. Kirschstein NRSA Postdoctoral Fellow
> >>>
> >>> Department of Pharmaceutical Sciences
> >>> School of Pharmacy
> >>> Health Sciences Facility II, Room 601
> >>> University of Maryland, Baltimore
> >>> 20 Penn St.
> >>> Baltimore, MD 21201
> >>>
> >>> jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> >>> http://mackerell.umaryland.edu/~jalemkul
> >>>
> >>> ==================================================
> >>> --
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> >>>
> > --
> > ==================================================
> >
> > Justin A. Lemkul, Ph.D.
> > Ruth L. Kirschstein NRSA Postdoctoral Fellow
> >
> > Department of Pharmaceutical Sciences
> > School of Pharmacy
> > Health Sciences Facility II, Room 601
> > University of Maryland, Baltimore
> > 20 Penn St.
> > Baltimore, MD 21201
> >
> > jalemkul at outerbanks.umaryland.edu | (410) 706-7441
> > http://mackerell.umaryland.edu/~jalemkul
> >
> > ==================================================
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>
>
>
> --
> João M. Damas
> PhD Student
> Protein Modelling Group
> ITQB-UNL, Oeiras, Portugal
> Tel:+351-214469613
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```