Thanks!
One question about amd + implicit solvent in my (loop refirement of
membrane protein) system
how it would be possible to take into account
Implicit solvent (I'm using gb models implemented in Amber) during
calculation of the alpha and Ethreshold values especially in case of
the second boost application where total number of atoms is taken into
account? In fact to calculate <Edihe> and <Epot> I need to perform
convectional MD without any restraints firstly. But because GB models
are the aproximation of the water (hight dielectric) the conformation
of the bundle (which should be in real in low dielectric medium) will
be perturbed during cMD run so I've obtained wrong (I guess very high)
values for both energy terms. Alternatively If I apply restraints on
bundle during cMD I obtained also wrong (lower) values for those
terms. In principle the same problems will be during aMD loop
refinement in water box (because to obtained boost values I need to
perform cMD firstly without any restraints on bundle).
TFH,
Gleb
2014-07-17 19:06 GMT+02:00 Carlos Simmerling <carlos.simmerling.gmail.com>:
> Compare to the published benchmarks to see if it's ok. Hard to directly
> compare explicit to implicit,, since cutoffs likely quite different.
> On Jul 17, 2014 12:34 PM, "James Starlight" <jmsstarlight.gmail.com>
> wrote:
>
> > some additional questions:
> > 1) I've noticed low performance in case of the GPU-simulation of my
> system
> > with the GB
> >
> > | Average timings for all steps:
> > | Elapsed(s) = 26775.49 Per Step(ms) = 13.37
> > | ns/day = 12.92 seconds/ns = 6687.18
> >
> > the same performance I have with the computation in explicit
> membrane-water
> > solvent for the same system. Does something wrong with CUDA simulation
> and
> > gb models?
> >
> > 2) in case of the usage of AMD with gb models how implicit solvent should
> > be taken into account in the computation of the total boost (where the
> > total number of atoms is used for the alpha and Ethreshold computation)
> >
> >
> > TFH,
> >
> > James
> >
> >
> > 2014-07-17 18:01 GMT+02:00 James Starlight <jmsstarlight.gmail.com>:
> >
> > > yes,
> > >
> > > but in my case no posres are applied on loops so I could prevent the
> > > rotation along peptide bond during its refirement with amd or other
> > energy
> > > boost added method.
> > >
> > > James
> > >
> > >
> > > 2014-07-17 14:00 GMT+02:00 Carlos Simmerling <
> > carlos.simmerling.gmail.com>
> > > :
> > >
> > > The amber gb models don't support membranes or dual dielectric regions.
> > You
> > >> could look into work by others like wonpil im.
> > >>
> > >> - there is no box, so volume is infinite and pressure not really
> > defined.
> > >> -if the positional restraints are strong, no dihedral restraints
> should
> > be
> > >> needed. You can add them, or just check as the run proceeds to make
> sure
> > >> those atoms aren't moving.
> > >> On Jul 17, 2014 7:50 AM, "James Starlight" <jmsstarlight.gmail.com>
> > >> wrote:
> > >>
> > >> > I think I have no more problems with the gb radii which I've found
> it
> > in
> > >> > the manual :) but the question with the
> > >> >
> > >> > 0) cut-offs is still exist because in case of in vacuum simulation I
> > use
> > >> > infitinive cutoffs but not sure what should I do in case of gb.
> > >> >
> > >> > Some additional question:
> > >> > 1) Does the simulation with gb support NPT besides NVT (I guess
> that
> > >> with
> > >> > the infinitive cutoffs it could be quite impossiblebut who knows:) )
> > >> >
> > >> > 2) I need to add restraints which will prohibit isomerisation of
> > peptide
> > >> > bond (it's needed in case of amd or sa simulations) in loops. In
> this
> > >> > simulation I've already frize all atoms of not-loops by means of
> > >> addition
> > >> >
> > >> > restraint_wt=10.0, restraintmask=':6-33,40-68,76-
> > >> > 109,120-143,177-204,216-246,256-286',
> > >> >
> > >> > so what should be provided besides to prevent rotation around omega
> > >> > dihedral angle?
> > >> >
> > >> >
> > >> > 3) Is there some additional options to GB for membrane protein
> > >> simulation
> > >> > w/o application of restrains to membrane-embedded part (assuming
> that
> > >> some
> > >> > part of protein should be in fact in water with di-electric 80 and
> > >> another
> > >> > in membrane with di-electirc= 2 )? How it could be taken into the
> > >> account
> > >> > in the GB simulation?
> > >> >
> > >> > TFH to everyone,
> > >> >
> > >> > James
> > >> >
> > >> >
> > >> > 2014-07-17 11:27 GMT+04:00 James Starlight <jmsstarlight.gmail.com
> >:
> > >> >
> > >> > > 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
> > >> > >> >
> > >> > >> _______________________________________________
> > >> > >> 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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> > >>
> > >
> > >
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> >
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Received on Thu Jul 17 2014 - 11:00:02 PDT
