[gmx-users] Doubt regarding membrane protein in POPC bilayer

Justin A. Lemkul jalemkul at vt.edu
Tue Mar 31 14:01:12 CEST 2009



Pawan Kumar wrote:
> Respected Sir,
> 
> Greetings from Pawan.
> Thanks for all your suggestions.
> Is it possible to use the lipid.itp file from Tieleman sir's website in 
> combination with GROMOS 96 force field without any modification ?

If you want to use lipid.itp without any modification, you are restricted to the 
ffgmx (deprecated!) force field.  For Gromos96-lipid.itp combination, simply 
remove the ";; parameters for lipid-GROMOS interactions," as these nonbonded 
combinations are for ffgmx only.  Otherwise, the nonbonded interactions (which 
now have consistent combination rules) should be generated correctly.

> Is it fine if I use the Gromos/Berger force field combination for the 
> system I am using ?

That is a decision you will have to make based on a thorough examination of the 
literature, and the benefits and criticisms of these particular force field 
parameters.

> I am sorry to ask this but can you please help me with some information 
> how to modify the lipid.itp file ?

That depends entirely upon what you want to do.  If you want Gromos/Berger, I've 
already told you.  If you want OPLS/modified Berger, search the archives for 
Chris Neale's posts on that topic.

-Justin

> I will edit vdwradii.dat file as per your suggestion.
> 
> 
> Thanking you,
> 
> Yours sincerely,
> Pawan
> 
> On Tue, Mar 31, 2009 at 4:53 PM, Justin A. Lemkul <jalemkul at vt.edu 
> <mailto:jalemkul at vt.edu>> wrote:
> 
> 
> 
>     Pawan Kumar wrote:
> 
>         Respected Sir,
> 
>         Greetings from Pawan.
>         I have edited the lipid.itp file to add just one line extra " H
>         atom from the opls_force_filed.itp " at the end of lipid
>         interactions data and that works fine.
>         I have done this after seeing the archives. It was given either
>         I should change the file for sigma and epsilon values or else
>         just add this line.
>         I think I have done it correctly. If not please correct me.
> 
> 
>     No, that is incorrect.  You need to add the additional atom type as
>     well as convert C6/C12 to sigma/epsilon.  Otherwise, the calculated
>     nonbonded interactions are meaningless.  Read instructions carefully!
> 
>     Force fields have to be internally self-consistent, so using the
>     parameters from OPLS with Berger lipids will give spurious results.
>      The only proper combinations are Gromos/Berger or OPLS/converted
>     Berger.
> 
> 
>         I have removed the position restraints after the inflategro
>         procedure.
>         After that I did energy minimization using define = -DFLEXIBLE.
>         I will change the temperature as per your suggestion.
>         I thought before solvating if I do position restraint mdrun the
>         lipids will compact more surrounding the protein.
> 
> 
>     No, your system will probably explode due to unsatisfied charge
>     interactions and hydrogen bonds.  There is a substantial dipole in
>     each lipid headgroup that can repel the lipids away from each other
>     if it is not shielded.
> 
> 
>         Thats the step when I got Lincs warnings and segmentation fault.
>         Then I tried solvating the system using genbox step and
>         spc216.gro as the solvent.
>         But before doing the solvation step I copied the vdwradii.dat
>         file into the working directory and increased the value for
>         carbon to 0.5.
>         But the result of this was " Segmentation fault " again. Can you
>         please tell me why I get the " Segmentation fault " here in this
>         step.
>         The command used was : genbox  -cp comp_em27.pdb -cs spc216.gro
>         -o box.pdb -p topol.top
> 
> 
>     Using a 0.5-nm radius for carbon will cause problems of excess
>     memory consumption, or otherwise breaks the calculation.  Use
>     something more along the lines of 0.35 or 0.375, and manually delete
>     out any stray waters in the hydrophobic core.
> 
>     -Justin
> 
> 
>         Thanking you,
> 
>         Yours sincerely,
>         Pawan
> 
>         On Tue, Mar 31, 2009 at 4:20 PM, Justin A. Lemkul
>         <jalemkul at vt.edu <mailto:jalemkul at vt.edu>
>         <mailto:jalemkul at vt.edu <mailto:jalemkul at vt.edu>>> wrote:
> 
> 
> 
>            Justin A. Lemkul wrote:
> 
> 
> 
>                Pawan Kumar wrote:
> 
>                    Respected Sir,
> 
>                    Greetings from Pawan.
>                    I have used force constants of 100000 in position
>         restraint
>                    .itp files for proteins as suggested in Dr. Tieleman' s
>                    webisite for Inflategro.
>                    The mdp files are :
> 
> 
>                The .mdp files look reasonable enough, although I don't
>         know why
>                you are applying position restraints during EM.  If it is for
>                InflateGRO, that is fine, but once the system is
>         assembled, you
>                should remove the position restraints from the protein to
>                minimize the system more.
> 
>                And are you sure you want 300K?  DPPC will be in a gel
>         phase at
>                that temperature.  If you want a more realistic fluid-phase
>                model, you'll have to go above 315K (323K is common).
> 
> 
>            One thing I just noticed.  You don't have solvent in your
>            position-restrained run?  That could be a big problem if the
>         lipid
>            headgroups are strongly repelled from one another.  Add solvent
>            before doing anything other than EM.
> 
>            -Justin
> 
> 
>                    *Topology file :*
>                    ; Include forcefield parameters
>                    #include "ffoplsaa.itp"
>                    #include "lipid.itp"
>                    #include "dppc.itp"
> 
> 
>                This section should not work, as written.  Have you modified
>                lipid.itp according to Chris Neale's half-epsilon
>                double-pairlist method?  If not, what you've done makes no
>                sense.  The Berger lipid parameters distributed through
>                Tieleman's site are designed for use with the Gromos force
>                fields.  They can be modified (search in the archives),
>         but that
>                can also be a source of error.  Users who have made
>         mistakes in
>                the conversion have seen their systems explode.
> 
>                -Justin
> 
>                    ; Include chain topologies
>                    #include "topol_A.itp"
>                    #include "topol_B.itp"
>                    #include "topol_C.itp"
> 
>                    ;#ifdef POSRES
>                    ;#include "lipid_posre.itp"
>                    ;#endif
> 
>                    ; Include water topology
>                    #ifdef FLEX_SPC
>                    #include "flexspc.itp"
>                    #else
>                    #include "spc.itp"
>                    #endif
> 
>                    #ifdef POSRES_WATER
>                    ; Position restraint for each water oxygen
>                    [ position_restraints ]
>                    ;  i funct       fcx        fcy        fcz
>                      1    1       1000       1000       1000
>                    #endif
> 
>                    ; Include generic topology for ions
>                    #include "ions.itp"
> 
>                    [ system ]
>                    ; Name
>                    PROTEIN IN DPPC BILAYER
> 
>                    [ molecules ]
>                    ; Compound      #mols
>                    Protein_A           1
>                    Protein_B           1
>                    Protein_C           1
>                    DPPC              926
>                    ;SOL             23552
> 
>                    Please help with some suggestions.
> 
>                    Thanking you,
> 
>                    Yours sincerely,
>                    Pawan
> 
>                    On Mon, Mar 30, 2009 at 6:22 PM, Justin A. Lemkul
>                    <jalemkul at vt.edu <mailto:jalemkul at vt.edu>
>         <mailto:jalemkul at vt.edu <mailto:jalemkul at vt.edu>>
>                    <mailto:jalemkul at vt.edu <mailto:jalemkul at vt.edu>
>         <mailto:jalemkul at vt.edu <mailto:jalemkul at vt.edu>>>> wrote:
>                                   Pawan Kumar wrote:
> 
>                           Respected Sir,
> 
>                           Greetings from Pawan.
>                           I did the Inflategro procedure for the POPC
>         bilayer
>                    generated
>                           using genconf.
>                           It took around 26 compressions for coming near the
>                    initial area
>                           (just above it).
>                           The minimization were all converged to Fmax <
>         1350.
>                           If I decrease the Fmax less than this I am getting
>                    machine
>                           precision.
>                           But when I proceeded with the final compressed
>                    structure for pr
>                           mdrun it gave lincs warnings and ended with
>                    segmentation fault.
>                           As an alternative to this bilayer I used the
>         DPPC bilayer
>                           (pre-equilibrated) which is given in GMX-Benchmark
>                    distribution.
>                           I carried out the same steps of Inflategro. I used
>                    the cutoff of
>                           14 A in the inflation and compression step also.
>                           In this case the the Steepest Descents
>         converged to
>                    Fmax < 1000
>                           in all the steps. The maximum force war never
>         above 850.
>                           But when I did position restraint mdrun with
>         the last
>                    compressed
>                           file I got Lincs warnings and Segementation fault
>                    after few
>                           steps (30 - 40 steps).
>                           Can you please help how to proceed ?
> 
> 
>                       If the minimization procedure is adequately finishing,
>                    then the
>                       problem comes from something you are doing.  If
>         you post
>                    your .mdp
>                       file, we may be able to see if there are any obvious
>                    mistakes.
> 
>                       -Justin
> 
>                           Thanking you,
> 
>                           Yours sincerely,
>                           Pawan
> 
> 
>                           Justin A. Lemkul
>                           Graduate Research Assistant
>                           ICTAS Doctoral Scholar
>                           Department of Biochemistry
>                           Virginia Tech
>                           Blacksburg, VA
>                           jalemkul[at]vt.edu <http://vt.edu>
>         <http://vt.edu> <http://vt.edu> |
> 
>                    (540) 231-9080
>                          
>         http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> 
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> 
>            --    ========================================
> 
>            Justin A. Lemkul
>            Graduate Research Assistant
>            ICTAS Doctoral Scholar
>            Department of Biochemistry
>            Virginia Tech
>            Blacksburg, VA
>            jalemkul[at]vt.edu <http://vt.edu> <http://vt.edu> | (540)
>         231-9080
>            http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
> 
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> 
>     -- 
>     ========================================
> 
>     Justin A. Lemkul
>     Graduate Research Assistant
>     ICTAS Doctoral Scholar
>     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
> 
>     ========================================
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> 
> 
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-- 
========================================

Justin A. Lemkul
Graduate Research Assistant
ICTAS Doctoral Scholar
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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