[gmx-users] Re: Simulation in the high temperature conditions
James Starlight
jmsstarlight at gmail.com
Thu Apr 12 08:45:38 CEST 2012
At the current stage I want to understand how to apply such disres in
relation to the current starting structure without external experimental
data.
E.g. I have some initial structure for wich I'd like to generate disres
applied on each backbone atom within some cutoff radius. As the consequence
I want that this set of disres were generated automatically assuming
deviation from this initial structure on the desired value ( as I
understood this is -disre_dist ). Does my understanding correct in general
? What is -dis_frac wich result in some shift on the defired value both of
up0 and up1 distances in the output file ?
I have complete some test run when I've applied disres in such manner with
-disre_dist 1 nm in the Rc=1nm to allow deviation of the backbone within
the same radius. As the consequence I've obtained deformed structure of my
protein. I've checked RMSD and found that deformation have occured very
rapidly but new non-native conformation was stabilised very quickly ( new
plato on rmsd diagram) and was relatively stabile during 15ns. Does the
disres were applied incorrectly or shoud I increase forses ? ( I've used
fc=100 )
James
James
11 апреля 2012 г. 23:31 пользователь Tsjerk Wassenaar
<tsjerkw at gmail.com>написал:
> Hey James,
>
> It's reassuring to find you did think of it. The approach may have
> merits, or may be a waste of CPU. But the proof of the pudding is in
> the eating of it. The connection with NMR data makes sense. The
> restraints may be time-averaged, involving different conformational
> states, hampering the usual annealing-based structure determination.
> But room-temperature simulations may not allow the transitions
> required. Hence, applying the same restraints at an elevated
> temperature, probably using a higher force constant, could yield the
> desired ensemble. To get a room-temperature ensemble by using some
> restraints will probably not work, but it's an interesting list of
> things that shouldn't have worked according to some, yet worked out
> for those who tried :p Nonetheless, applying local restraints to
> maintain integrity and use an elevated temperature to enhance
> conformational sampling, might actually also be a valuable approach.
> Good luck :)
>
> Tsjerk
>
> On Wed, Apr 11, 2012 at 8:27 PM, James Starlight <jmsstarlight at gmail.com>
> wrote:
> > Tsjerk,
> >
> >
> > As Justin already has noticed there were lot of examples of
> implementation
> > of the high temperature aproach to increase conformation sampling. This
> > could be usefull because of short time-scale of typical MD trajectory and
> > hight energy barriers of the adjacent energy-minimums wich could
> correspond
> > to the functional-relevant conformations. So the main reason of such
> > stimulations in to dicrease such barriers to promote transitions to the
> > functional-relevant states conformations Finally I can sample the output
> of
> > such simulation and compare this resulted conformations with the
> > experimental data. If I obtain good similarity this may indicate about
> > efficiency of such aproach
> >
> > On other hand such simulation could result in some non-native
> conformations
> > due to the non-native condtions. So the artificial restrains like as the
> > distance restrains within native conformation ( obttained by NMR for
> > instance) could be usefull-aproach to keep the system in the native-like
> > conformations while enhansing sampling of the native-like structures via
> > rising of temperatures. So combinations of such tricks could give
> > physical-relevant results partly couldn't it ? However I suppose that the
> > main disadvantage of such aproach is the non-physical intermediate states
> > produced by non-native transitions pathways wich could arrise from such
> > simulation.
> >
> >
> >
> > James
> >
> > 11 апреля 2012 г. 18:09 пользователь Tsjerk Wassenaar <tsjerkw at gmail.com
> >
> > написал:
> >
> >> Hey James,
> >>
> >> Have you thought about the physical relevance of your results?
> >>
> >> Cheers,
> >>
> >> Tsjerk
> >>
> >> On Wed, Apr 11, 2012 at 12:01 PM, James Starlight
> >> <jmsstarlight at gmail.com> wrote:
> >> > Tsjerk,
> >> >
> >> > Thank you for suggestions!
> >> >
> >> >
> >> > Indeed the hight temperature ( I'm using 700K) which I use for
> enhansing
> >> > sampling rate resulted in destabilisation of the secondary structure.
> >> >
> >> > To prevent this I've used two slightly different aproaches based on
> the
> >> > restraint. But in both cases I've used slightly soft restrains with
> >> > fs=10-200.
> >> >
> >> > The first aproach is the ussage of the posres applied on each backbone
> >> > atom
> >> > with fc=10-50. I've tested case with fc=50 and found that such
> restrains
> >> > were very hight. I've not noticed any conformation sampling of my
> >> > protein (
> >> > rmsd of backbone < 0.3 nm) during 10ns of such simulation. So I've
> >> > decided
> >> > to test a case with fc=10 ( under calculation)
> >> >
> >> > The second approach is the application of the harmonic distance
> >> > restrainse
> >> > wich I've applied on each backbone atom pair in the CUTOFF radius of
> 1.0
> >> > nm.
> >> > The Rc value was chosen because of my protein is the 7 buddle of alpha
> >> > helices so this aproach could be usefull but exactly value for R have
> >> > been
> >> > chosen empirically. I've selected deviation value wich are equal to
> 1\2
> >> > of
> >> > cutoff radius = 1.5 nm. I have not realise whaat I could obtain yet
> from
> >> > this because I'm not quite sure about coccect values of such disres.
> >> >
> >> >
> >> > James
> >> >
> >> > 11 апреля 2012 г. 13:35 пользователь Tsjerk Wassenaar
> >> > <tsjerkw at gmail.com>
> >> > написал:
> >> >>
> >> >> Hey :)
> >> >>
> >> >> I'd say a protein should be loosing structure at 700K. Can't even say
> >> >> the force field is wrong there, even though it hasn't been
> >> >> parameterized for such temperatures for certain. You'd have to check
> >> >> with experiments.
> >> >> Trying to do high-temperature simulations is fine. But trying to do
> >> >> high temperature simulations to get results that match a room/body
> >> >> temperature ensemble is completely bogus. If you aim to use this
> >> >> approach for enhanced sampling, you're in for some serious
> >> >> reparameterization. Part of the deal may indeed be adding
> >> >> long(er)-range distance restraints. However, the force constants to
> >> >> use will increase with temperature, and with very high temperatures
> >> >> the force constants may end up so high that they give rise to fast
> >> >> oscillations, which will require using a smaller time step.
> >> >>
> >> >> Just my 2 cents...
> >> >>
> >> >> Tsjerk
> >> >>
> >> >> --
> >> >> Tsjerk A. Wassenaar, Ph.D.
> >> >>
> >> >> post-doctoral researcher
> >> >> Molecular Dynamics Group
> >> >> * Groningen Institute for Biomolecular Research and Biotechnology
> >> >> * Zernike Institute for Advanced Materials
> >> >> University of Groningen
> >> >> The Netherlands
> >> >> --
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> >> >
> >> >
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> >>
> >> --
> >> Tsjerk A. Wassenaar, Ph.D.
> >>
> >> post-doctoral researcher
> >> Molecular Dynamics Group
> >> * Groningen Institute for Biomolecular Research and Biotechnology
> >> * Zernike Institute for Advanced Materials
> >> University of Groningen
> >> The Netherlands
> >> --
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>
>
> --
> Tsjerk A. Wassenaar, Ph.D.
>
> post-doctoral researcher
> Molecular Dynamics Group
> * Groningen Institute for Biomolecular Research and Biotechnology
> * Zernike Institute for Advanced Materials
> University of Groningen
> The Netherlands
> --
> gmx-users mailing list gmx-users at gromacs.org
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