[gmx-users] Coarse-grained Protein-ligand simulations

[Mac Kevin Braza]

Thank you Prof. Lemkul,

I appreciate your comment on this part.

Sir Peter Kroon,

We want to do the coarse-grained MD simulation to access long timescale
events of the
effect of the ligand binding to the GPCR, at least microsecond . For now,
the most accessible means for us is to
do the CGMD. But we are currently being cornered in choosing which set-up
will best suit, and
if it will allow us to see these events. We are looking also in the
possibility of coarse-graining
the ligand, and if you can share your expertise in coarse-graining also the
ligand that would be great.
I appreciate this Sir Kroon, thank you very much!

Best regards,
Mac Kevin E. Braza

On Mon, Apr 1, 2019 at 5:07 PM Peter Kroon <p.c.kroon at rug.nl> wrote:

> If I may chip in: It really depends on what you're studying, and what
> forcefield you're using to do it. Unfortunately there is no FF that
> reproduces all behaviour accurately. The art is in picking one that (at
> least) reproduces what you're interested in.
>
>
> Peter
>
> On 29-03-19 17:26, Justin Lemkul wrote:
> >
> >
> > On 3/29/19 9:17 AM, Mac Kevin Braza wrote:
> >> Thank you Professor Lemkul,
> >>
> >> But would you suggest on how can I coarse-grained the ligand I am
> >> using? I
> >> have been searching resources online but they do not work in our part.
> >
> > I don't work with CG simulations, so I'm not much help. I would think
> > that a CG parametrization of a ligand would remove all the detail
> > you'd normally want to see in terms of ligand-protein interactions.
> >
> > -Justin
> >
> >> I hope you can help us. Thank you Prof. Lemkul!
> >>
> >> Best regards,
> >> Mac Kevin E. Braza
> >>
> >> On Fri, Mar 29, 2019, 8:59 PM Justin Lemkul <jalemkul at vt.edu> wrote:
> >>
> >>>
> >>> On 3/29/19 3:32 AM, Mac Kevin Braza wrote:
> >>>> Hello everyone,
> >>>>
> >>>> I am simulating a coarse-grained model of a membrane protein (GPCR) in
> >>>> lipid bilayer and an all-atom ligand octopamine. I build the protein,
> >>>> solutes, and membrane in the web server CHARMM-GUI. While, I added the
> >>>> ligand to the protein complex manually using the same coordinates
> >>>> of the
> >>>> coarse-grained protein model.
> >>>>
> >>>> I used the GROMACS input files from the output of CHARMM-GUI to
> >>>> simulate
> >>>> the system. I include the LIGAND.ITP (from the PRODRG Server) to the
> >>>> system.top and added the atom indexes in the index.ndx file.
> >>> Don't do this. An atomistic representation of a ligand and a CG
> >>> representation of everything else is incompatible. Mixing and matching
> >>> force fields is never a good idea. Moreover, PRODRG produces topologies
> >>> that are known to be unsuitable for MD simulations.
> >>>
> >>>> However, when I proceed with the second part of equilibration, the
> >>>> following errors occurred.
> >>>>
> >>>> *Command line*:
> >>>>     gmx grompp -f step6.2_equilibration.mdp -o
> >>>> step6.2_equilibration.tpr
> >>> -c
> >>>> step6.1_equilibration.gro -p system.top -n index.ndx
> >>>>
> >>>> Setting the LD random seed to 1722366284
> >>>> Generated 2391 of the 4656 non-bonded parameter combinations
> >>>> Excluding 1 bonded neighbours molecule type 'PROA_P'
> >>>> Excluding 1 bonded neighbours molecule type 'POPC'
> >>>> Excluding 1 bonded neighbours molecule type 'W'
> >>>> Excluding 1 bonded neighbours molecule type 'NA'
> >>>> Excluding 1 bonded neighbours molecule type 'CL'
> >>>> Excluding 3 bonded neighbours molecule type 'LIG'
> >>>> Velocities were taken from a Maxwell distribution at 303.15 K
> >>>> Removing all charge groups because cutoff-scheme=Verlet
> >>>>
> >>>> -------------------------------------------------------
> >>>> Program gmx grompp, VERSION 5.1.4
> >>>> Source code file:
> >>>> /home/gromacs-5.1.4/src/gromacs/gmxpreprocess/readir.c,
> >>>> line: 2690
> >>>>
> >>>> Fatal error:
> >>>> 20 atoms are not part of any of the T-Coupling groups
> >>>> For more information and tips for troubleshooting, please check the
> >>> GROMACS
> >>>> website at http://www.gromacs.org/Documentation/Errors
> >>>> -------------------------------------------------------
> >>>>
> >>>> The 20 atoms described the ligand I placed inside the protein-membrane
> >>>> complex. I want to know if where can this error originate and how
> >>>> can we
> >>>> fix them?
> >>> This simply means you haven't specified the ligand anywhere in tc-grps.
> >>> But again, back up and reevaluate your approach, which is far more
> >>> problematic than this simple index group issue.
> >>>
> >>> -Justin
> >>>
> >>> --
> >>> ==================================================
> >>>
> >>> Justin A. Lemkul, Ph.D.
> >>> Assistant Professor
> >>> Office: 301 Fralin Hall
> >>> Lab: 303 Engel Hall
> >>>
> >>> Virginia Tech Department of Biochemistry
> >>> 340 West Campus Dr.
> >>> Blacksburg, VA 24061
> >>>
> >>> jalemkul at vt.edu | (540) 231-3129
> >>> http://www.thelemkullab.com
> >>>
> >>> ==================================================
> >>>
> >>> --
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