Re: [gmx-users] Problem with Gromacs and Charmm force field dump rates

[Mark Abraham]

OK, sounds suspicious.

Hopefully you have some of these already, but I suggest you prepare two run
inputs
* macromolecule in a T-coupling group and water in a T-coupling group
* macromolecule in a T-coupling group and water+sugar in a T-coupling group
and run each .tpr at the two different dump rates. I don't think the
flavour of T-coupling is relevant. Assuming the results reproduce your
observations, please open an issue at https://redmine.gromacs.org/ and
attach the two .tpr and four .log files e.g. in a tarball file.

Thanks!

Mark

On Thu, Feb 8, 2018 at 3:47 PM Vivien WALTER 
wrote:

> Hi Mark,
>
> Thank you for the swift reply.
>
> Sorry for not being clear enough. As I tried to explain in my previous
> mail, the problem comes from the behavior of the sugar molecules regarding
> the macromolecule, not just from the box size (which I only used as an
> example on the first mail to explain we had a divergence in the results).
>
> At high dump rates, the saccharide adsorbs on the macromolecule, while at
> low dump rates the saccharide desorbs from it.
> We ran several tests to try to understand the problem further. Here is one
> example : if I take the resulting system of the high dump rate simulation
> (sugar adsorbed) and restart from this configuration with the same high
> dump rate, the sugar stays adsorbed. This behavior was confirmed on several
> restart.
> If I take the same system (high dump rate / sugar adsorbed) and this time
> change the dump rate to the low one, the sugar will desorb from it during
> the first simulation. And I can restart it, still with the low dump rate,
> the sugar will not adsorb back.
>
> This trend in the saccharide-macromolecule interactions was observed on
> several systems with different number of saccharide molecules in the box,
> but also at different temperatures. And it's always the same: at high dump
> rate, the sugar adsorbs, but desorbs at low dump rate.
>
> I hope the problem is more clear now.
>
> Best regards,
> Vivien
>
> --
> Dr. Vivien WALTER
> 
> Institut Charles Sadron
> 23, Rue du Loess
> 
> BP 84047
> 67034 STRASBOURG CEDEX 2, France
> 
> tel: +33(0)388 414 113
> fax: +33(0)388 414 099
> --
> Gromacs Users mailing list
>
> * Please search the archive at
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> posting!
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Re: [gmx-users] Problem with Gromacs and Charmm force field dump rates

[Vivien WALTER]

Hi Mark,

Thank you for the swift reply.

Sorry for not being clear enough. As I tried to explain in my previous
mail, the problem comes from the behavior of the sugar molecules regarding
the macromolecule, not just from the box size (which I only used as an
example on the first mail to explain we had a divergence in the results).

At high dump rates, the saccharide adsorbs on the macromolecule, while at
low dump rates the saccharide desorbs from it.
We ran several tests to try to understand the problem further. Here is one
example : if I take the resulting system of the high dump rate simulation
(sugar adsorbed) and restart from this configuration with the same high
dump rate, the sugar stays adsorbed. This behavior was confirmed on several
restart.
If I take the same system (high dump rate / sugar adsorbed) and this time
change the dump rate to the low one, the sugar will desorb from it during
the first simulation. And I can restart it, still with the low dump rate,
the sugar will not adsorb back.

This trend in the saccharide-macromolecule interactions was observed on
several systems with different number of saccharide molecules in the box,
but also at different temperatures. And it's always the same: at high dump
rate, the sugar adsorbs, but desorbs at low dump rate.

I hope the problem is more clear now.

Best regards,
Vivien

-- 
Dr. Vivien WALTER

Institut Charles Sadron
23, Rue du Loess
BP 84047
67034 STRASBOURG CEDEX 2, France

tel: +33(0)388 414 113
fax: +33(0)388 414 099
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Re: [gmx-users] Problem with Gromacs and Charmm force field dump rates

[Mark Abraham]

Hi,

One simulation at each dump rate doesn't lead to a reliable conclusion that
the change in volume may be related to the dump rate, because if you run
replicates at each dump rate, they would not reproduce each other. If you
run such replicates and there is, or is not, a consistent trend, then that
can suggest the presence (respectively, absence) of a connection between
volume change and dump rate.

Mark

On Thu, Feb 8, 2018 at 3:01 PM Vivien WALTER 
wrote:

> Hi Peter,
>
> Thank you for the swift reply. Here are some details about your answers. I
> hope the problem will appear more clear with them.
>
> > Increase/decrease by how much? Is it converged?
> The results completely diverge, that is the problem. The interactions we
> are observing through the simulations are in opposition: attraction with
> high dump rates (25000 steps) or repulsion with low dump rates (2500
> steps), hence the change in box size. This is why we are confused about
> these simulations.
>
> > Don't do this (http://www.gromacs.org/Documentation/Terminology/
> Thermostats)
> We use two coupling groups: one for the sugar molecules and the solvent
> (water), and the one for a macromolecule interacting with the sugar.
>
> > Simulations perfomed by Gromacs are not binary reproducible, so you will
> > (never) get exactly the same result twice starting from the same point.
> > This is inherent in how the simulation is performed.
> > http://www.gromacs.org/Documentation/Terminology/Reproducibility
> > This is why sampling is so important, to show that the fluctuations you
> > see average out and are not depending on stochastic errors or the
> > starting conformation.
> Similar answer than in the first point: the problem are not the
> fluctuations between measurements leading to the same average result, but
> the complete divergence between the behiavors at low and high dump rates.
>
> Best regards,
> Vivien
>
> --
> Dr. Vivien WALTER
> 
> Institut Charles Sadron
> 
> 23, Rue du Loess
> BP 84047
> 67034 STRASBOURG CEDEX 2, France
> 
> tel: +33(0)388 414 113
> fax: +33(0)388 414 099
> --
> Gromacs Users mailing list
>
> * Please search the archive at
> http://www.gromacs.org/Support/Mailing_Lists/GMX-Users_List before
> posting!
>
> * Can't post? Read http://www.gromacs.org/Support/Mailing_Lists
>
> * For (un)subscribe requests visit
> https://maillist.sys.kth.se/mailman/listinfo/gromacs.org_gmx-users or
> send a mail to gmx-users-requ...@gromacs.org.
>
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Re: [gmx-users] Problem with Gromacs and Charmm force field dump rates

[Vivien WALTER]

Hi Peter,

Thank you for the swift reply. Here are some details about your answers. I
hope the problem will appear more clear with them.

> Increase/decrease by how much? Is it converged?
The results completely diverge, that is the problem. The interactions we
are observing through the simulations are in opposition: attraction with
high dump rates (25000 steps) or repulsion with low dump rates (2500
steps), hence the change in box size. This is why we are confused about
these simulations.

> Don't do this (http://www.gromacs.org/Documentation/Terminology/
Thermostats)
We use two coupling groups: one for the sugar molecules and the solvent
(water), and the one for a macromolecule interacting with the sugar.

> Simulations perfomed by Gromacs are not binary reproducible, so you will
> (never) get exactly the same result twice starting from the same point.
> This is inherent in how the simulation is performed.
> http://www.gromacs.org/Documentation/Terminology/Reproducibility
> This is why sampling is so important, to show that the fluctuations you
> see average out and are not depending on stochastic errors or the
> starting conformation.
Similar answer than in the first point: the problem are not the
fluctuations between measurements leading to the same average result, but
the complete divergence between the behiavors at low and high dump rates.

Best regards,
Vivien

-- 
Dr. Vivien WALTER

Institut Charles Sadron
23, Rue du Loess
BP 84047
67034 STRASBOURG CEDEX 2, France

tel: +33(0)388 414 113
fax: +33(0)388 414 099
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Re: [gmx-users] Problem with Gromacs and Charmm force field dump rates

[Peter Kroon]

Hi Vivien,


My answers are inline


On 08-02-18 12:28, Vivien WALTER wrote:
> Dear all,
>
> We are experiencing a strange problem with all-atom simulations using
> Gromacs and Charmm force field, and we have trouble to sort it out.
>
> We are simulating a single-ring sugar and we observe radically different
> behaviors of the molecule as a function of the simulation dump rate.
> Starting from the same .gro file with continuation = yes (so using the same
> initial velocities written in the file), the interactions of the sugar with
> its surroundings is different between two simulations if the following set
> of parameters are changed: nstxout, nstvout, nstenergy and nstlog. Between
> the two .mdp files, absolutely no other parameters are changed. As an
> example of what differs between the simulation, the box size along X and Y
> axis are increasing with low dump rates (2500 steps) but decreases with
> high dump rates (25000 steps).
Increase/decrease by how much? Is it converged?
>
> We tried to reproduce the problem with a box filled with only water
> molecules, but in this configuration there is no difference between our
> results when different dump rates are used. Following the previous example,
> the evolutions of the box size superimpose perfectly for different dump
> rate.
> We tried to change the conformation of the sugar to see if it would have an
> impact on the problem observed, but the problem remains.
>
> The forcefield used is Charmm36 (version from june 2015) and Gromacs
> version is 2016.4. For the sugar, the structure file was constructed
> according to the more stable chair conformation of the saccharide, but the
> force field of the molecule was directly taken from the standard Charmm
> force field parameters. Water model used is TIP3P.
> For the simulation parameters, the pressure coupling used is a
> semi-isotropic Parrinello-Rahman set at 1.0 bar in both directions
> (compressibility 4.5e-5 and tau_p equals to 2.0). For the temperature
> coupling, we used first V-Rescale, but as we suspected the stochastic
> process to lead to different results for different dump rates, we also
> tried a Nose-Hoover thermostat. In both cases, the three molecular groups
> are coupled separately at the same temperature and the same tau_t (0.4)
Don't do this (http://www.gromacs.org/Documentation/Terminology/Thermostats)
> The rest of the main options for the .mdp file are taken from the
> recommanded parameters for using Charmm36 in Gromacs (
> http://www.gromacs.org/Documentation/Terminology/Force_Fields/CHARMM )
>
> Is it a known problem of Gromacs using Charmm36? Is there a way to fix the
> problem and obtain identical results, or at least similar evolutions?
Simulations perfomed by Gromacs are not binary reproducible, so you will
(never) get exactly the same result twice starting from the same point.
This is inherent in how the simulation is performed.
http://www.gromacs.org/Documentation/Terminology/Reproducibility
This is why sampling is so important, to show that the fluctuations you
see average out and are not depending on stochastic errors or the
starting conformation.
>
> Thanks you in advance for your help,
> Best regards,
> Vivien WALTER
>
Peter

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