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
Received on Thu Jul 10 2014 - 03:00:02 PDT
