[gmx-users] how to deal with LINCS warnings despite prolonged stabilization of the system?

[Anna Marabotti]

Dear Mark,
thank you very much for your answer. I'll try to do what you suggest, 
but what makes me crazy is that when the simulation stops, I have no 
indication at all about what happens to the system (or at least, I don't 
know how to search for these indications). I'd like to understand what 
happens to my system, to avoid groping like a blind.

Following suggestions in 
http://www.gromacs.org/Documentation/Terminology/Blowing_Up, I analysed 
the following energetic terms that in my opinion should give me an 
indication of the variation of the intramolecular energy: Angle - Proper 
Dih - Improper Dih - LJ14 - Coulomb 14 - LJ (SR) - LJ (LR) - 
Disper.corr. - Coulomb (SR) - Coul. recip.- Constr. rmsd - Total - 
Potential - Kinetic - Temperature - Pressure - all the Coul, LJ 14, 
LJ-LR, LJ-SR: Prot-PRot, Prot-nonProt, nonProt-nonProt. For NONE of 
these energetic terms I found something anomalous (for example, the 
"spikes"), and the order of magnitude of these energetic values are 
comparable with the ones of the system that successfully completed the 
simulations. Did I monitor the correct parameters, or not? What should I 
expect to see for such problems?

Another question: if the system is "blowing up" should I see an 
"explosion-like" behaviour visualizing the trajectories, or not? At 
present, the only thing I see is the jump over periodic boundaries, but 
I don't think it's exactly the same.

Final question: for your experience, can a bad parameterization of the 
protein ligand influence not only the ligand itself but also the protein 
determining the starting of LINCS WARNINGS on atoms that apparently are 
(relatively) far from the ligand?

Thanks a lot
Anna

______________________________________________
Anna Marabotti, Ph.D.
Assistant Professor
Department of Chemistry and Biology
University of Salerno
Via Giovanni Paolo II, 132
84084 Fisciano (SA)
Italy
Phone: +39 089 969583
Fax: +39 089 969603
E-mail: amarabotti at unisa.it
Skype: annam1972
Web page: http://www.unisa.it/docenti/annamarabotti/index

"Indifference is the eighth deadly sin" (don Andrea Gallo)

Il 03/07/2013 12:00, gmx-users-request at gromacs.org ha scritto:
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Message: 3 Date: Wed, 3 Jul 2013 11:15:25 +0200 From: Mark Abraham 
<mark.j.abraham at gmail.com> Subject: Re: [gmx-users] how to deal with 
LINCS warnings despite prolonged stabilization of the system? To: 
Discussion list for GROMACS users <gmx-users at gromacs.org> Message-ID: 
<CAMNuMAQgsk7giNO3MdiGtVt2xukzA+cYovky7bQcxzpTXkgsJg at mail.gmail.com> 
Content-Type: text/plain; charset=ISO-8859-1 This kind of instability 
boils down to "if the starting configuration and model physics are 
capable of running a stable simulation, you're being too rough with it" 
- as http://www.gromacs.org/Documentation/Terminology/Blowing_Up says 
using different words. Each time one changes the ensemble, that's rough. 
Using position restraints can be useful while getting the temperature 
close to right, but just switching them off can be too rough. Consider 
lowering the force constant over several stages. Switch barostat 
algorithm only when restraints have been off in the previous stage. For 
that matter, each time step is rough - use a smaller one for 
equilibration than for production. 0.5fs can be necessary while things 
stabilize. Or turn off constraints temporarily and go even shorter. Mark 
On Wed, Jul 3, 2013 at 10:52 AM, Anna Marabotti <amarabotti at unisa.it> 
wrote:

> Dear all,
> I'm writing again because I really need to understand what more can I do on
> my systems that are still dealing with LINCS warnings. I minimized further
> the systems (from emtol 500 to emtol 100) and the final potential energies
> and max force were nearly identical to those I obtained when emtol was set
> to 500, in my opinion this indicates that the system has already converged
> to a minimum. I made a NVT (thermostat: V-rescale) for 100 ps and a NPT
> (thermostat: V-rescale and barostat: Berendsen) for 1 ns, and I checked the
> energies of the system: all was regular without any apparent perturbation. I
> then started the production run in NPT ensemble (thermostat: V-rescale and
> barostat: Parrinello-Rahman or Berendsen - I tried both of them) and approx.
> after 10-15 ns my system turns on LINCS WARNINGS (but never at the same
> time), and sometimes produces many stepXXXXX.pdb files, stopping the
> simulation. When I look at the energies of the system, I don't see anything
> strange apart the fact that the graph is interrupted. When I see the
> simulations with VMD, I don't see anything strange apart some crossings of
> the periodic boundaries (I don't see any system "exploding" or so on). I
> have the doubt that the cofactor could be badly parameterized, but LINCS
> WARNINGS do not involve only the cofactor, but also the protein backbone
> (the cofactor is covalently bound to protein backbone, but LINCS WARNINGS do
> not involve the parts of protein directly bound to the cofactor: would it be
> possible such an effect when only the cofactor is badly parameterized?)
> Please give me some suggestions. I read documentation in GROMACS web site,
> but I did all I saw, apart for skipping LINCS WARNING, including the
> analysis of the g_energy terms and comparison with the simulations that went
> well. I don't see any significant difference (if somebody wants to see, I
> can provide the files)
>
> Thanks a lot
> Anna