From: Norman Geist (norman.geist_at_uni-greifswald.de)
Date: Fri Jun 01 2012 - 01:33:48 CDT
Hi Vincent,
thank you very much for your detailed mail.
> -----Ursprüngliche Nachricht-----
> Von: owner-namd-l_at_ks.uiuc.edu [mailto:owner-namd-l_at_ks.uiuc.edu] Im
> Auftrag von Vincent Leroux
> Gesendet: Donnerstag, 31. Mai 2012 17:41
> An: Norman Geist
> Cc: namd-l_at_ks.uiuc.edu
> Betreff: Re: AW: AW: namd-l: NAMD feature request Hydrogenscale
>
> Hi Norman,
>
> Of course a timestep of 4 fs for electrostatics will harm energy
> conservation, but usually not critically so. You may try to increase
> cutoff distances to see if that minimizes the problem, but you may lose
> a good part of the speed increase in the process. But frankly, correct
> me if I am mistaken, there is not much you can do about that, this is
> bound to integrator stability and this is the price to pay for
> timesteps larger than 1 fs. If you are worried about a 1 K/ns
> temperature raise, Langevin NVT dynamics may solve the problem with
> just a very small damping factor (such as 0.01), so you introduce
> temperature control as lightly as possible. The temperature will
> fluctuate slightly around the target but this should be acceptable.
> Another workaround would be velocity rescaling with large intervals
> (e.g. 1 ns) but you have to be careful of the "hot solvent cold solute"
> issue then. At this point, you may wonder what is best between this and
> a neat NVE equilibrium production run !
> with 1 fs timesteps, but 3-4x less accessible simulation time. Depends
> on what you want to see.
That would be a compromise but also decreases speed if I remember correctly. Usually one tries to run the production runs uncontrolled but I guess the langevin won't harm the thermo dynamic no much.
But here's exactly what I mean. One sets the fullelectfrequency to 4 and harms energy conservation. And now you say it's ok to react with a little thermostat control. So why I may not react on too fast hydrogens when increasing the timestep in your opinion?
>
> And frankly, I am fundamentally not convinced by hydrogen mass
> repartitioning. Question of philosophy, maybe, but the CHARMM and AMBER
I see ^^
Well I think many people wasn't also convinced from the shake algorithm when it was introduced and it is nearly the same as the hydrogens degrees of freedom are reduced. And as the mass only effects the transfer of forces to atom velocities, and not directly the forces themselves, it's a good "trick" aswell as rigidbonds.
> FFs were carefully parameterized against reference QM data with
> "normal" protons. It may look like heavier protons are an easy way to
No not really. If you look through the parameter files you will see that most atom types are just copies with other names. They were not parameterized for special molecules or molecular environments. They are the same for all amino acids no matter which molecule or molecule chain. Also I already saw that some predefined residues hydrogens are all the same charge. So most of it is not really special parameterized. And the bond/angle/torsion/etc. force constants and potentials are again defined against these non special atom types. The only thing that is special, most of cases, is the partial charge.
To parameterize the new heavy hydrogens would change the forcefield, but that’s not the target. The target is to keep the chemical environment untouched, but remove some degrees of freedom from the hydrogens as rigidbonds does the same and everybody is using it. Nobody would care if the hydrogen would vibrate within the trajectory, but the decrease of speed while not using shake convinces most people to use it. I think I it worth to implement it for tests as I don't think it's too difficult for the developers to integrate. And then see if the behavior is good or not.
> increase simulation speed while (apparently) conserving energy, but
> IMHO if you fall for it you move your model further away from reality
> to the point it is now quite unphysical, and you will pay a price for
> that too. In the best case scenario, I guess you will simply mess up
> the H-bond networks at biomolecular interfaces, especially those
> involving waters.
Are you talking about the "extremely realistic" TIP3P model, where the H-O-H Angle is _fixed_ and an additional H-H bond secures the whole molecule? As we are simulating collagen triple helices, where the hbonds are really important, we could try the scientific value of the method if it would be implemented.
But forcefield parameters are interdependent to a
> very large extent: change some atomic masses, and I bet you have to re-
> parameterize a lot of other parameters, which is downright crazy. The
> CHARMM or AMBER devs may better warn you against that better than me,
> or at least describe precisely what to expect and not to expect from
> this trick.
>
> If you do not like the protons moving too much why not try an unified-
> atom FF? It will by nature tolerate larger timesteps. There are other
> "maybe good enough" solutions for faster simulations that do not
> involve changing physical constants. Implicit solvent is the most
> obvious, and some AMBER forcefields seem quite good at that. The recent
> Molly approach from NAMD may be appropriate, have not tried it yet. If
> you want the best conformational exploration possible unbiased MD may
> also not be the optimal strategy.
The fact that the hydrogens are moving "TOO" much, indicates that exactly this is the unrealistic part of the simulation that one needs to be reacted on. It is at least as unrealistic that the hydrogens move that fast that they rip apart the molecules as making the hydrogens a _really_ little heavier.
Regards
Norman
>
> Regards
> VL
>
>
> ----- Mail original -----
> > De: "Norman Geist" <norman.geist_at_uni-greifswald.de>
> > À: "Vincent Leroux" <vincent.leroux_at_loria.fr>
> > Cc: "Namd Mailing List" <namd-l_at_ks.uiuc.edu>
> > Envoyé: Jeudi 31 Mai 2012 08:06:29
> > Objet: AW: AW: namd-l: NAMD feature request Hydrogenscale
> >
> > > -----Ursprüngliche Nachricht-----
> > > Von: owner-namd-l_at_ks.uiuc.edu [mailto:owner-namd-l_at_ks.uiuc.edu] Im
> > > Auftrag von Vincent Leroux
> > > Gesendet: Mittwoch, 30. Mai 2012 17:28
> > > An: namd-l_at_ks.uiuc.edu
> > > Betreff: Re: AW: namd-l: NAMD feature request Hydrogenscale
> > >
> > > Excuse me, the fact that a method is published does not prevent me
> > > to
> > > criticize it.
> >
> > Hopefully not. No opinion, no progress.
> >
> > >
> > > Well, if you do not want to compute more timesteps than required,
> > > then
> > > why don't you use r-RESPA-based multiple timestepping (nonbonded 2
> > > and
> > > fullelectfrequency 4 can work very well on your typical
> > > protein-protein
> > > or protein-ligand system provided careful equilibration was done)
> > > and
> > > the Molly method as recently implemented in NAMD?
> >
> > I'm already using fullelectfrequency 4 for better speedup through the
> > gpus, but that harms my energy conservation and my system increase
> > temperature by about 0.5K-1K per ns.
> >
> > >
> > > This looks IMHO a little bit more serious than just changing atom
> > > masses
> >
> > Question of philosophy. I don't think calculating non-bonded and
> > electrostatic forces with atom positions that are no more true is
> > better.
> >
> > > while using a forcefield that was not parameterized against these
> > > new
> > > unnatural values. In the reference you provide, it is just
> > > mentioned
> > > such a trick only moderately affects the viscosity in a TIP3P water
> > > box,
> > > you have to go to the original reference from the people that
> > > actually
> > > had the idea to get some serious validation attempts:
> > > http://dx.doi.org/10.1002/(SICI)1096-987X(199906)20:8<786::AID-
> > > JCC5>3.0.CO;2-B
> >
> > Please read more carefully. The viscosity change of the water was a
> > side effect, not the effect that was targeted.
> >
> > >
> > > You will see that the gain in performance is not so high, without
> > > resorting to additional tricks, and that the effect of the
> > > dynamical
> > > behavior of the simulated system is not negligible...
> >
> > That's not true. Without additional tricks a timestep of 4fs is
> > possible only with the hydrogen mass repartitioning, 4 times higher
> > than namds default 1fs.
> >
> > >
> > > Do you still think this is a good idea? If you wish, go ahead and
> > > ask
> >
> > Yes.
> >
> > > the CHARMM forcefield developers their opinion... this is
> > > especially
> >
> > In fact I use the amber ff.
> >
> > > relevant since according to the Berendsen paper hydrogen mass
> > > repartitioning only works well if piled up with dummy atoms usage,
> >
> > Not true. This only provides the possibility of even higher timesteps
> > than 4fs.
> >
> > > requiring some additional tinkering with the force field itself, so
> > > that
> > > the dihedrals are not messed up... So you need a kind of forcefield
> > > able
> > > to tolerate that. That would certainly be more GROMOS than CHARMM.
> > >
> > > Regards
> > > VL
> > >
> > >
> > > On 30/05/2012 16:17, Norman Geist wrote:
> > > > And of course a link to the publication of this method as it is
> > > already used.
> > > >
> > > > Accelerating Biomolecular Dynamics in the Microsecond Time Scale
> > > > http://pubs.acs.org/doi/full/10.1021/ct9000685
> > > >
> > > > A little more serious please.
> > > > Why should I compute every timestep if I don't need it.
> > > >
> > > > Norman Geist.
> > > >
> > > >> -----Ursprüngliche Nachricht-----
> > > >> Von: owner-namd-l_at_ks.uiuc.edu [mailto:owner-namd-l_at_ks.uiuc.edu]
> > > >> Im
> > > >> Auftrag von Vincent Leroux
> > > >> Gesendet: Mittwoch, 30. Mai 2012 15:04
> > > >> An: namd-l_at_ks.uiuc.edu
> > > >> Betreff: Re: namd-l: NAMD feature request Hydrogenscale
> > > >>
> > > >> Focusing on the potential "scientific value" of making all
> > > >> hydrogens
> > > 4x
> > > >> heavier for the sake of getting MD "just run faster with big
> > > >> timesteps",
> > > >> how about passing the idea to the CHARMM forcefield developers
> > > >> in
> > > the
> > > >> dedicated mailing list? ;-)
> > > >>
> > > >>
> > > >>
> > > >> On 30/05/2012 14:14, Axel Kohlmeyer wrote:
> > > >>> On Wed, May 30, 2012 at 7:16 AM, Ajasja Ljubetič
> > > >>> <ajasja.ljubetic_at_gmail.com> wrote:
> > > >>>>> without commenting on scientific value,
> > > >>>>
> > > >>>>
> > > >>>> Could we hear this comment as well? (If it is not to vulgar,
> > > >>>> of
> > > >> course:)
> > > >>>
> > > >>> since i have no proper justification for
> > > >>> it, i'd rather not. the world is already
> > > >>> full of too many prejudices and people
> > > >>> with half-knowledge or no knowledge
> > > >>> blasting out opinions and speculations.
> > > >>>
> > > >>> axel.
> > > >>>
> > > >>>>
> > > >>>> Best regards,
> > > >>>> Ajasja
> > > >>>
> > > >>>
> > > >>>
> > > >
> > > >
> >
> >
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