ram bio wrote:
Dear Justin,
As i generated the protein-ligand docked complex using opls FF, for the
consistency, i am trying to use opls ff generated ligand parameters
during md simulations in lipid bi layer. I found that MKTOP can generate
topology files using opls ff for small molecules.
I understand that. The program did a poor job, per the reasons I cited before.
I do not know anything about mktop (other than what it does), so I cannot
analyze its suitability here, but due to missing parameters and bogus charges,
you should not use that topology for anything.
I have also tried swiss param to generate the ligand parameters to be
used in protein ligand simulation using gromacs. The force field i am
using for simulations is OPLS. My ligand contains an azido group and a
tropane ring with protonated nitrogen. SwissParam force field has been
designed to be compatible with the Charmm force field, but they are not
tested on opls.Using the ligand topologies from swissparam, i was able
to run the MD simulations using gromacs with opls without errors
(swissparam - gromacs tutorial), only issues being the charges on the
ligand, so i generated various input files (mol2 files) for swissparam
with charges generated using ambcc1, gastergier and MMFF. But the itp
files obtained from swissparam had same charges for the ligand atoms
irrespective of the input provided i.e. charged or uncharged mol2 files, and
If SwissParam was designed to be used with CHARMM, the most intuitive next step
is to use CHARMM for the MD, is it not? I understand the point about trying to
keep the force fields consistent between docking and MD, but it may not be
feasible (i.e., there may not be suitable parameters in OPLS for the bizarre
functional groups you're dealing with).
As per Gromacs website:
"Note that an .itp file
<http://www.gromacs.org/Documentation/File_Formats/.itp_File> will be
specific to a given force field, and will only function when included by
a .top file
<http://www.gromacs.org/Documentation/File_Formats/.top_File> that has
previously included the .itp files
<http://www.gromacs.org/Documentation/File_Formats/.itp_File> for that
force field. Appropriate use of the |#define| and |#ifdef| mechanisms
can permit the same .itp file
<http://www.gromacs.org/Documentation/File_Formats/.itp_File> to work
with multiple force fields, e.g. |share/top/water.itp|."
Note the key caveat here - through the use of #define and #ifdef you can make
use of different force fields. That means you can control which parameters are
applied based on different conditions. I could write an .itp file for any
molecule that has force field parameters for any force field, and all I'd have
to do is enclose all relevant directives within #ifdef blocks and it would work.
This note does *not* indicate that you can mix and match force fields. Doing
so is generally a very bad idea, if it even works syntactically.
so, i think even though the swissparam generated topologies based on
MMFF fit to charmm (based on testing), they could also be used with
opls. It was informed by swiss param team that the ligand parameters
generated by swissparam could also be used with opls FF in principle as
they are based on MMFF
So, in order to cross check or validate my results i was trying to use
mktop to generate the ligand topologies for MD simulations.
Maybe the SwissParam-generated topology will work. There are commonalities
underlying these force fields, to be sure. Still, the methodology for properly
deriving OPLS parameters is quite well described in the literature, right down
to the QM basis sets required to run the geometry optimizations and charge
calculations.
-Justin
Please let me know your comments and suggestions on the procedure ,
regarding the compatibility of MMFF generated topologies to be used by
OPLS and other methods to validate my results.
Thanks,
Pramod
On Wed, Oct 12, 2011 at 1:28 PM, Justin A. Lemkul <jalem...@vt.edu
<mailto:jalem...@vt.edu>> wrote:
ram bio wrote:
Dear Justin,
Thanks for the information.
Initially, i just wanted to run a simulation of protein-ligand
in water solvent . I renamed the topology.top generated from
mktop to ligand.itp; and included the ligand.itp line in the
topol.top file generated from the pdb2gmx. During the pdb2gmx
command, i used opls FF. The coordinates of ligand used as
input for mktop were added to the output of pdb2gmx (process.pdb
- only protein coordinates), so that the structure file along
with ligand coordinates (processlig.pdb) can be used for further
steps. I doubt whether the procedure followed by me is correct,
as when i execute grompp command to add ions i am getting errors :
grompp -f ions.mdp -c procentsolv.gro -p topol.top -o ions.tpr
ERROR 1 [file ligand.itp, line 291]:
No default Ryckaert-Bell. types
..........
------------------------------__-------------------------
Program grompp, VERSION 4.5.4
Source code file: toppush.c, line: 1526
Fatal error:
[ file ligand.itp, line 397 ]:
Atom index (0) in dihedrals out of bounds (1-53).
This probably means that you have inserted topology section
"dihedrals"
in a part belonging to a different molecule than you intended to.
In that case move the "dihedrals" section to the right molecule.
For more information and tips for troubleshooting, please check
the GROMACS
website at http://www.gromacs.org/__Documentation/Errors
<http://www.gromacs.org/Documentation/Errors>
------------------------------__-------------------------
The commands executed to reach the grompp step are as follows:
pdb2gmx -f jhcdyinteractionposea.pdb -ignh -o process.pdb
editconf -f processlig.pdb -o procent.pdb -princ
editconf -f procent.pdb -o procent.gro -c -d 1.0 -bt cubic
genbox -cp procent.gro -cs spc216.gro -o procentsolv.gro -p
topol.top
grompp -f ions.mdp -c procentsolv.gro -p topol.top -o ions.tpr
I have attached the topol.top, ligand.itp and procentsolv.gro
files for your information, Please let me know your suggestions
to fix this error.
The ligand.itp file is trash. Most of your atoms have zero charge
(except for a few that have +/- 1...yikes!) and on line 397 (as
cited in the error message) atom 0 is referenced, which of course
does not exist, since numbering starts with 1. You also have some
exotic atom types present, and thus bonded parameters cannot be
assigned, as grompp complained earlier.
You need a better quality topology, and perhaps a different force
field that might be suited for doing these simulations.
-Justin
Thanks,
Pramod
On Wed, Oct 12, 2011 at 12:38 PM, Justin A. Lemkul
<jalem...@vt.edu <mailto:jalem...@vt.edu>
<mailto:jalem...@vt.edu <mailto:jalem...@vt.edu>>> wrote:
ram bio wrote:
Dear Gromacs Users,
I am using opls FF for my protein-ligand simulations in lipid
bilayer. I have generated the topologies for the ligand
using
MKtop. The output from the MKTOP gives the top file, but
not the
coordinate/structure file. Please let me know if any
tutorial is
available for merging the output of mktop into gromacs MD
simulation.
You can #include any molecule topology in a system .top, provided
you have the right format:
http://www.gromacs.org/____Documentation/File_Formats/.____itp_File
<http://www.gromacs.org/__Documentation/File_Formats/.__itp_File>
<http://www.gromacs.org/__Documentation/File_Formats/.__itp_File
<http://www.gromacs.org/Documentation/File_Formats/.itp_File>>
There is no tutorial for using mktop with a
protein-ligand/membrane
system, but there are tutorials for protein-ligand complexes:
http://www.bevanlab.biochem.____vt.edu/Pages/Personal/justin/____gmx-tutorials/complex/index.____html
<http://vt.edu/Pages/Personal/justin/__gmx-tutorials/complex/index.__html>
<http://www.bevanlab.biochem.__vt.edu/Pages/Personal/justin/__gmx-tutorials/complex/index.__html
<http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/complex/index.html>>
and membrane protein systems:
http://www.bevanlab.biochem.____vt.edu/Pages/Personal/justin/____gmx-tutorials/membrane_____protein/index.html
<http://vt.edu/Pages/Personal/justin/__gmx-tutorials/membrane___protein/index.html>
<http://www.bevanlab.biochem.__vt.edu/Pages/Personal/justin/__gmx-tutorials/membrane___protein/index.html
<http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/membrane_protein/index.html>>
-Justin
-- ==============================____==========
Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
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Virginia Tech
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Department of Biochemistry
Virginia Tech
Blacksburg, VA
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