Thanks for suggestion!
Do you think that gb 8 model (in comparison to other gb models) might be
best solution for membrane protein with frozen *membrane embedded* elements
of its secondary structure? Some technical questions:
1)should I use infinitive cutoffs (999) during IS simulation ?
2) I'm not sure If I assigned gb radii correctly - does it should be done
explicitly during processing of my model by tleap ? Are there special
values for the membrane proteins might be?
TFH,
James
2014-07-16 17:37 GMT+02:00 Carlos Simmerling <carlos.simmerling.gmail.com>:
> I think that if you choose a reasonably accurate GB model then this task is
> much easier than with explicit water. Explicit may be more accurate, but
> sampling loop conformational changes can be too slow. You always have to
> trade off accuracy and sampling. I would suggest giving our igb=8 model a
> try (read the manual for suggestions on radii, etc). As always, you'll want
> to make sure you have some data against which you can validate any
> predictions that you make about structure. Regarding the REMD part, it's
> another good reason to give GB a try. REMD in explicit water is expensive
> (many replicas) and quite slow. Freezing part could be a problem- I'm not
> sure if you can do that in all of the Amber MD codes (using the GB pmemd
> code is probably best). You could choose positional restraints on the
> non-loop region to keep it fixed. Having it be totaly frozen might not be
> good anyway, since there may be some adjustment needed for different loop
> options.
>
> Another possibility is to use loop modeling that doesn't involve MD - such
> as the analytical approaches. Then you might rescore the various models
> with a good MM+GBSA approach.
> good luck
> CS
>
>
> On Thu, Jul 10, 2014 at 5:44 AM, James Starlight <jmsstarlight.gmail.com>
> wrote:
>
> > some suggestions.
> >
> > some people gave me evidence that for my task (see a full set of loop
> > confirmations and chose most probable) it will not good to use implicit
> > solvent +amd because this will produce very unphysical thermodynamics
> isn't
> > it?
> >
> > In fact I'm dealing with the membrane protein where membrane-embeded part
> > should be fixed (I would not refine something here) and loops which are
> > exposed to the solvent must be free to move. In this regards I've tried
> to
> > applied gb model of IS with the frozen of not refined part of my protein.
> > Will it be reasonable to use REMD with such implicit solvent model for
> the
> > refinement? How It could be possible to really simplify REMD protocol for
> > such loop prediction (e,g using small number of replicas or not).
> > Some another suggestion (e.g brut force md with gb models)?
> >
> > James
> >
> >
> >
> > 2014-07-09 12:01 GMT+02:00 James Starlight <jmsstarlight.gmail.com>:
> >
> > > some updating of my issue
> > >
> > > I need to refine regions of my model consisted of water exposed 10-15
> > > residues loops in which I'm not certain after its homology modeling.
> For
> > > this task I'd like to
> > > 1) Freeze all atoms of the protein consisted of the secondary structure
> > > elements in which I'm not interest.
> > > 2)Use some implicit solvent model for this simulation.
> > > 3) Use some enhancing sampling technique to sample all possible
> > > conformation of the loops at short timescale but keeping initial
> > > thermodynamics of the system => predict possible folding in the loops
> > > during the refinement.
> > >
> > > please suggest me possible GB implicit solvent model as well as
> enhanced
> > > sampling engine (I'm chosing between replica exchange and accelerated
> md
> > > with dihedral boost only). Any additional methods?
> > >
> > > I'll be very thankful to all,
> > >
> > >
> > > James
> > >
> > >
> > > 2014-06-14 22:21 GMT+02:00 James Starlight <jmsstarlight.gmail.com>:
> > >
> > > Also I'll be thankful if someone check my example SA script with
> applied
> > >> multiple position restraints to some segment of my protein (here I'd
> > like
> > >> to freeze all atoms but not loop which I'd like to sample).
> > >>
> > >> SA with posres
> > >> &cntrl
> > >> imin=0,
> > >> ntx=1,
> > >> irest=0,
> > >> ntc=2,
> > >> ntf=2,
> > >> tol=0.0000001,
> > >> nstlim=50000,
> > >> ntt=3,
> > >> gamma_ln=1.0,
> > >> ntr=1,
> > >> ig=-1,
> > >> ntpr=100,
> > >> ntwr=10000,
> > >> ntwx=100,
> > >> dt=0.002,
> > >> nmropt=1,
> > >> ntb=0,
> > >> ntp=0,
> > >> cut=999.0,
> > >> ioutfm=1,
> > >> ntxo=2,
> > >> igb=1,
> > >> /
> > >> &wt
> > >> type='TEMP0',
> > >> istep1=0,
> > >> istep2=10000,
> > >> value1=0.0,
> > >> value2=103.0 /
> > >> &wt
> > >> type='TEMP0',
> > >> istep1=10001,
> > >> istep2=20000,
> > >> value1=103.0,
> > >> value2=203.0 /
> > >> &wt
> > >> type='TEMP0',
> > >> istep1=20001,
> > >> istep2=50000,
> > >> value1=203.0,
> > >> value2=303.0 /
> > >> &wt type='END' /
> > >> fixed
> > >> 1000.0
> > >> RES 1 67
> > >> END
> > >> fixed
> > >> 1000.0
> > >> RES 75 142
> > >> END
> > >> fixed
> > >> 1000.0
> > >> RES 169 241
> > >> END
> > >> fixed
> > >> 1000.0
> > >> RES 249 286
> > >> END
> > >> END
> > >>
> > >>
> > >> Here I try to heat my system in 3 subsequent steps performing
> simulation
> > >> using implicit solvent without PBC. Does it correct in general? I
> could
> > not
> > >> visualize my system in VMD using
> > >> vmd -parm7 b2ar_Amber.prmtop -netcdf sa.nc
> > >> what should I fix here?
> > >>
> > >>
> > >> James
> > >>
> > >>
> > >> 2014-06-13 23:50 GMT+04:00 James Starlight <jmsstarlight.gmail.com>:
> > >>
> > >> Dear Vlad,
> > >>>
> > >>>
> > >>> many thanks for suggestions. I've already seen some papers describing
> > >>> some methodologies of structural refinement based of some enhanced
> > sampling
> > >>> methods. However in case of loop refinement what could be expected
> > from the
> > >>> brute-force md with aplied restraints on the rest of the protein
> > (excluding
> > >>> refined loops) using 1) implicit solvent 2) some
> > high-temperatutre-based
> > >>> method like simulating annealing.
> > >>>
> > >>> James
> > >>>
> > >>>
> > >>> 2014-05-28 11:53 GMT+04:00 Vlad Cojocaru <
> > >>> vlad.cojocaru.mpi-muenster.mpg.de>:
> > >>>
> > >>> Dear James,
> > >>>>
> > >>>> I am afraid you'd have to do some reading ... Its very hard to
> believe
> > >>>> that somebody on this list has the time to give you detailed
> > >>>> instructions. What you ask for is a summary of many different
> papers.
> > >>>> The Amber manual has an example of simulated annealing protocol for
> > NMR
> > >>>> refinement which used to be with distance dependent dielectric
> (maybe
> > it
> > >>>> has changed in the meantime). Anyhow, you'd have to adapt that to
> the
> > >>>> implicit solvent model you wish to use. The implicit solvent models
> > are
> > >>>> all well documented in the corresponding publications which are
> > >>>> referenced in the Amber manual.
> > >>>>
> > >>>> Besides, take care how you interpret your results. The longer the
> > loops,
> > >>>> the less you can rely on the loop refinement. You'd need to run a
> > number
> > >>>> of different simulations, maybe even test different force fields ...
> > >>>> Especially if loops are functionally important, you may easily draw
> > >>>> wrong conclusions from such refinements. Comparison with experiments
> > is
> > >>>> always good.
> > >>>>
> > >>>> Best,
> > >>>> Vlad
> > >>>>
> > >>>>
> > >>>> On 05/28/2014 09:29 AM, James Starlight wrote:
> > >>>> > I try to specify my question.
> > >>>> >
> > >>>> > I suppose that force field based simulated annealing with
> positions
> > >>>> > restraints applied to the all protein atoms but not for loops
> which
> > >>>> I'd
> > >>>> > like to refine might be exactly what I'm looking for. Could
> someone
> > >>>> suggest
> > >>>> > appropriate SA setups for such loop refirement: e.g I'm
> interesting
> > in
> > >>>> > number of SA windows, coupling constants in each windows,
> > appropriate
> > >>>> > implicit solvent models?
> > >>>> >
> > >>>> >
> > >>>> > James
> > >>>> >
> > >>>> >
> > >>>> > 2014-05-26 14:06 GMT+04:00 James Starlight <
> jmsstarlight.gmail.com
> > >:
> > >>>> >
> > >>>> >> Dear Amber's users!
> > >>>> >>
> > >>>> >>
> > >>>> >> I need to refine some flexible regions (mainly long loop and
> linker
> > >>>> >> regions) of my proteins prior to the production MD run using some
> > >>>> enhanced
> > >>>> >> sampling engines implemented in Amber like accelerated molecular
> > >>>> dynamics
> > >>>> >> or simulated annealing. Please provide me with some basic ideas
> of
> > >>>> the
> > >>>> >> easiliest realization of these methods in amber including
> suitable
> > >>>> implicit
> > >>>> >> solvent models for such task with the tutorials and further
> > reading.
> > >>>> >>
> > >>>> >>
> > >>>> >> TFH,
> > >>>> >>
> > >>>> >> James
> > >>>> >>
> > >>>> > _______________________________________________
> > >>>> > AMBER mailing list
> > >>>> > AMBER.ambermd.org
> > >>>> > http://lists.ambermd.org/mailman/listinfo/amber
> > >>>> >
> > >>>>
> > >>>> --
> > >>>> Dr. Vlad Cojocaru
> > >>>> Max Planck Institute for Molecular Biomedicine
> > >>>> Department of Cell and Developmental Biology
> > >>>> Röntgenstrasse 20, 48149 Münster, Germany
> > >>>> Tel: +49-251-70365-324; Fax: +49-251-70365-399
> > >>>> Email: vlad.cojocaru[at]mpi-muenster.mpg.de
> > >>>>
> > >>>>
> > >>>> _______________________________________________
> > >>>> AMBER mailing list
> > >>>> AMBER.ambermd.org
> > >>>> http://lists.ambermd.org/mailman/listinfo/amber
> > >>>>
> > >>>
> > >>>
> > >>
> > >
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
> _______________________________________________
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Received on Thu Jul 17 2014 - 00:30:03 PDT
