[gmx-users] minimization -- bugzilla or general advice?

[David Mobley]

Dear Christian,

>  mmh, just my 0.02€: I guess in a very rough energy landscape (as in
>  solvated peptides or proteins) this is not generally true, because
>  with small steps the system might get stuck in the next tiny local
>  minimum, while with a larger step size it may jump across it.
>  And I guess exactly this happens in your failing simulations: Your
>  system is stuck in a local minimum high up on the slopes of the energy
>  funnel. I guess this is just normal and happens some times. You might
>  alter the system by a little modeling (move the problematic atoms
>  slightly), or try -DFLEXIBLE, or perhaps rather increase step size.
>  Double precision minimization has proved to be more stable for me in
>  problematic cases, like straightening out a skewed average structure
>  of a trajectory.

If the system is truly in a local minimum, the force should be small,
right, since the force is by definition zero at any minimum (local or
otherwise)? I agree there may be situations in which the *energy* may
still be very unfavorable after minimization, but the forces should be
small.

I should note that I never have these problems (incomplete
minimization) with any other simulation package I use, so I strongly
suspect that the problem is something that GROMACS in particular is
doing in minimization, and *not* just a general problem with
minimizing on a high-dimensional landscape.

David

>  Regards
>
>  Christian
>
>
>
>
>  > Thanks,
>  > David
>  >
>  >
>  >>  Best
>  >>  XAvier
>  >>
>  >>
>  >>
>  >>  > I often have problems with minimization in gromacs, but now I think I
>  >>  > have something a little more systematic to say.
>  >>  >
>  >>  >First, my system: I am simulating a short peptide in a mix of two
>  >>  > co-solvents. I use a program called packmol which can start pack
>  >>  > specified number of molecules into a box of specified size, with a
>  >>  > specified distance tolerance between atoms, to generate starting gro
>  >>  > files. I am simulating a number of variants of this peptide in various
>  >>  > mixes of the two co-solvents (one of which is water).
>  >>  >
>  >>  > The problem I am having is that, even in double precision, gromacs
>  >>  > fails to properly minimize some of the systems -- minimization using
>  >>  > any of the minimizers I've tried (including steepest descents, my
>  >>  > preference) often terminates early (i.e. after ~50 steps) even in
>  >>  > double precision, leaving really large forces on some of the atoms
>  >>  > (usually 10^10 or more). The largest forces are usually on one atom of
>  >>  > a water molecule. Hence, when I plug the minimized output into
>  >>  > equilibration, my simulations explode due to large forces.
>  >>  >
>  >>  > Small tweaks to the system can change whether minimization works
>  >>  > properly or not in some cases -- for example, switching from double
>  >>  > precision to single precision will make some systems which fail in
>  >>  > double minimize properly, as will changing cutoffs. I assume also
>  >>  > things like changing architectures will allow some systems to minimize
>  >>  > (I've seen this behavior in the past).
>  >>  >
>  >>  > The problem is, I can find no combination of settings which will allow
>  >>  > *all* of my systems to minimize properly. Inevitably some fail, and I
>  >>  > end up having to go in by hand, look at the minimization log file, see
>  >>  > which water molecule has the huge force on it, and tweak its position
>  >>  > slightly by hand in the input gro file. Typically then minimization
>  >>  > will proceed just fine.
>  >>  >
>  >>  > This brings me to my question: Are the minimization algorithms
>  >>  > truncating some of the forces at some threshold value or something?
>  >>  > That is, why does minimization often end even though forces are still
>  >>  > huge?
>  >>  >
>  >>  > Currently, I'm using steepest descents with constraints turned off,
>  >>  > double precision, and emstep = 1.0e-8. I'm using Gromacs 3.3.2, rlist
>  >>  > = 0.9 = rcoulomb, rvdw-switch = 0.75 and rvdw = 0.8, pme_order 4,
>  >>  > ewald_rtol = 1e-04, and fourierspacing = 0.12, DispCorr = AllEnerPres,
>  >>  > and switched vdw.
>  >>  >
>  >>  > Any tips will be appreciated. Having to tweak coordinates by hand (or
>  >>  > write a script to do it) to get things to minimize isn't really a
>  >>  > satisfactory solution for me.
>  >>  >
>  >>  > I could submit a bugzilla, but I imagine what will happen if I submit
>  >>  > the cases that don't work for me is that they'll work fine for whoever
>  >>  > addresses the bugzilla and so this won't be regarded as a real
>  >>  > problem. Alternatively I could submit a whole slate of starting system
>  >>  > configurations and someone can debug just the ones that fail for them.
>  >>  >
>  >>  > Thanks,
>  >>  > David
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>  >>
>  >>  -----------------------------------------------------
>  >>  XAvier Periole - PhD
>  >>
>  >>  NMR & Molecular Dynamics Group
>  >>  University of Groningen
>  >>  The Netherlands
>  >>  http://md.chem.rug.nl/~periole
>  >>  -----------------------------------------------------
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