[gmx-users] Force Field for Vacuum simulation
Peter C. Lai
pcl at uab.edu
Thu Feb 2 11:10:25 CET 2012
On 2012-02-02 11:57:22AM +0300, James Starlight wrote:
> Peter,
>
> Yes the main reason is the CPU economy for such experiment. My current
> experiment consist of investigation of the tight paking forces (primarily
> vdv effect) in the membrane receptor by inclusion of some point mutations.
>
>
> Actyally I think that simple biphastic system ( like in the Justin tutorial
> but with vacum layer instead of cyclohexane) is exactly that I need. How I
> could make such layers system where water dont move into the middle layer?
>
>
> James
The main issue is that vacuum is not a phase. Vacuum is simply empty space.
A particle's interaciton with vacuum is null, by definition so a
"biphasic" system with one of the "phases" being nothing is literally not
comparable to a true biphasic system. You have to realize this from a
physical point of view... Moreover, how do you know for certain that the
hydrophobic interaction between TM and lipid does not contribute to the
TM bundle packing and the interactions you are trying to study? Remember,
it has been shown that TMs "may flex to satisfy hydrophobic mismatch".
(Yeagle, et al Biochim Biophys Acta. 2007 Mar;1768(3):530-7)
Is using united-atom bilayer (Berger lipids, from Justin's KALP-15/DPPC
tutorial) still computationally unacceptable for you? (Tieleman et al 2006
J. Phys.: Condens. Matter 18 S1221). I did mention earlier also adding some
coupling parameters to use a coarse-grained bilayer with all-atom protein
too.
Anyway, if you are really adamant about not using explicit bilayer,
I thought about this a little. Maybe try using explicit waters in the non-
membrane portions of the system, then use implicit solvent (GBSA) with
the correct dielectric to mimic a hydrophobic phase....
I have no methodology for this approach.
If I were to take your request of "How do I use explicit water but vacuum"
literally: An all-atom system that preserves the vacuum in the membrane region
of the system would involve making a 2 walls of immobile waters:
You select a monolayer of waters at each end that you want to act as the
wall. Rename them to a different residue name in your .gro file. Reorder
the .gro file so that all the wall-water atoms are in their own contiguous
section. Copy the .itp you use for the mobile waters to another .itp, edit
and change the moleculetype to your wall residue name. Add the new .itp
to your .top. Either use freeze_grps or position restraints on the wall
oxygens to prevent them from moving. This approach has many many problems
associated with it, not least that of: "what do you do with the waters
in the solvent accessible space" and the fact that since there is vaccum
surrounding the outside of the TM bundle and waters inside the TM bundle,
your protein may explode from the lateral motion of the waters inside the
solvent accessible spaces pushing against the TMs...
>
>
>
>
>
> 2012/1/30 Peter C. Lai <pcl at uab.edu>
>
> > I am not sure of the actual interpretive value of such a methodology.
> > Are you just trying to save computational time by not having to simulate
> > an all atom bilayer? The solvent layer is going to contribute to the
> > majority of the computation cost in the first place. As an example, the
> > bilayer we are using for GPCR work consisting of 238 POPC molecules adds
> > 30552 atoms out of a total of 99547 atoms, In any case, people have been
> > conducting all-atom simulations of opsins since at least 2005 because
> > of the availability of computational resources. See: Lemaitre V., Yeagle,
> > P.,
> > Watts, A. Biochemistry 2005, 44, 12667-12680 . So it is unlikely that
> > any reviewers today will accept an opsin system simulated in anything but.
> >
> > Perhaps a biphasic implicit solvent model would work better for you (unsure
> > if gromacs can support an "exterior" dielectric and an interior
> > dielectric).
> > There may also be some people using a coarse-grained bilayer with an
> > all-atom
> > protein, but again, unless you have carefully determined the coupling
> > parameters between a MARTINI bilayer and an all-atom protein, there will
> > be doubts about the usefulness of such a system.
> >
> > If you really must do without the bilayer, you might be able to get away
> > with using strong i,i+4 distance constraints within your TMs to preserve
> > helical stability while the entire protein is solvated.
> >
> >
> > On 2012-01-30 10:50:35AM +0400, James Starlight wrote:
> > > David, Justin
> > >
> > > Thanks again for help!
> > >
> > >
> > > I have just few questions about in vacum sumulation of membrane proteins.
> > >
> > >
> > > I want to simulate GPCR receptor wich have big transmembrane ( helix)
> > > domain and some connecting loop regions wich are exposed to the solvent.
> > >
> > > As I understood in classical vacum simulation all charges must be redused
> > > to avoid its collapse.
> > >
> > > I want to build biphastic system water-vacum-water where loops would be
> > in
> > > water and TM helixes in vacum region.
> > >
> > > Something like this I've read in old publications about simulation of
> > > bacteriorhodopsin http://ukpmc.ac.uk/abstract/MED/10412722
> > >
> > >
> > > 1- Could you tell me where I could found possible algorithm about builing
> > > of such water-vacum-water system?
> > >
> > > 2- Also I'd like to specify what should I do with the charges residues.
> > I'd
> > > like to use AMBER-like or OPLS ff for such simulation As I understood I
> > > must neitralize only charges in TM helices and keep residues in LOOP
> > > intact. Might this aproache be correct?
> > >
> > >
> > > James
> > >
> > > 2012/1/29 David van der Spoel <spoel at xray.bmc.uu.se>
> > >
> > > > On 2012-01-29 17:09, James Starlight wrote:
> > > >
> > > >> Hi, Justin.
> > > >>
> > > >> Yes. The GFP chromophore is a part of backbone. It's formed from Ser
> > Tyr
> > > >> Gly by cyclisation of the Ser with Gly and subsequent dehydrotation.
> > As
> > > >> the consequence the mature chromophore has cyclised structure wich
> > named
> > > >> as the CRO residue in PDB structure.
> > > >>
> > > >> I've made for this CRO residue topology via PRODG server for GROMOS
> > ff.
> > > >>
> > > >> Than I've imported that new chromophore.top into the topology.top of
> > my
> > > >> structure in accordance to your tutorial.
> > > >>
> > > >> Finally I've merged CRO.gro and protein.gro ( I've cut CRO from the
> > pdb
> > > >> for creation of the topoogy for my protein via pdb2gmx)
> > > >>
> > > >> Than I've done minimisation and chromophore have been diffused from my
> > > >> protein :) It seems that I must add covalent bond between CRO and
> > > >> protein into the topology. But how I could do it for my multi topology
> > > >> file ?
> > > >>
> > > >
> > > > You need to add the bonds angles etc. The easiest way would be to make
> > a
> > > > special bond (specbond.dat file). You need an rtp entry for your cro
> > group
> > > > as well. Then pdb2gmx makes the necessary bonds.
> > > >
> > > > Of course you can make all the bonds, angles, diehdrals and pairs
> > manually
> > > > as well, but that is tedious and error prone.
> > > >
> > > >>
> > > >> James
> > > >>
> > > >> 2012/1/29 Justin A. Lemkul <jalemkul at vt.edu <mailto:jalemkul at vt.edu>>
> > > >>
> > > >>
> > > >>
> > > >>
> > > >> James Starlight wrote:
> > > >>
> > > >> Hi David!
> > > >>
> > > >> Thanks for reference I'll study it carefully.
> > > >>
> > > >>
> > > >> I have some general question about the vacuum simulation
> > > >>
> > > >> 1- I've found that common GROMOS fields are not suitable for
> > the
> > > >> vacuum simulation because of its implementation for condensed
> > > >> phase .
> > > >> But In some referencces I've found that people use 53.6 ff for
> > > >> the in
> > > >> vacuum simulation. In addition Ive done minimisation and
> > > >> equilibration
> > > >> in that ff in vacuum and my system have not been collapse :) Is
> > > >> there
> > > >> any wy to adopt this ff for the in vacum ?
> > > >>
> > > >> 2- I have uncommon onject for simulation. It's GFP protein
> > where
> > > >> chromophore group ( like ligand) is covalent bonded to the
> > > >> backbone of
> > > >> this protein. As I've understood in Justins tutorial there are
> > > >> no any
> > > >> covalent bonds between protein and ligand. But how I could make
> > > >> this
> > > >> bond if I operate with TWO topology files ( one for
> > chromophore and
> > > >> another for protein itself) ? I've done all steps in
> > accordance to
> > > >> Justins tutorial but on the minimisation step my chromphore
> > dissuse
> > > >> out of the protein interior because of absent of backbone
> > group.
> > > >>
> > > >>
> > > >> The GFP chromophore is part of the backbone of the protein, is it
> > not?
> > > >>
> > > >> The tutorial I have for a protein-ligand complex should not be
> > taken
> > > >> to mean that all non-protein entities are physically separate
> > > >> entities. Plenty of cofactors, chromophores, and the like are
> > > >> covalently attached to the protein.
> > > >>
> > > >> -Justin
> > > >>
> > > >> --
> > > >> ==============================**__==========
> > > >>
> > > >>
> > > >> Justin A. Lemkul
> > > >> Ph.D. Candidate
> > > >> ICTAS Doctoral Scholar
> > > >> MILES-IGERT Trainee
> > > >> Department of Biochemistry
> > > >> Virginia Tech
> > > >> Blacksburg, VA
> > > >> jalemkul[at]vt.edu <http://vt.edu> | (540) 231-9080
> > > >> http://www.bevanlab.biochem.__**vt.edu/Pages/Personal/justin<
> > http://vt.edu/Pages/Personal/justin>
> > > >> <http://www.bevanlab.biochem.**vt.edu/Pages/Personal/justin<
> > http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin>
> > > >> >
> > > >>
> > > >> ==============================**__==========
> > > >>
> > > >>
> > > >> --
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> > > >
> > > > --
> > > > David van der Spoel, Ph.D., Professor of Biology
> > > > Dept. of Cell & Molec. Biol., Uppsala University.
> > > > Box 596, 75124 Uppsala, Sweden. Phone: +46184714205.
> > > > spoel at xray.bmc.uu.se http://folding.bmc.uu.se
> > > > --
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> > --
> > ==================================================================
> > Peter C. Lai | University of Alabama-Birmingham
> > Programmer/Analyst | KAUL 752A
> > Genetics, Div. of Research | 705 South 20th Street
> > pcl at uab.edu | Birmingham AL 35294-4461
> > (205) 690-0808 |
> > ==================================================================
> >
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--
==================================================================
Peter C. Lai | University of Alabama-Birmingham
Programmer/Analyst | KAUL 752A
Genetics, Div. of Research | 705 South 20th Street
pcl at uab.edu | Birmingham AL 35294-4461
(205) 690-0808 |
==================================================================
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