[gmx-users] ' LONEPAIR LP1 ' gives error message in protein - ligand simulation

[Adarsh V. K.]

Dear all,

A ligand molecule (lig) contains a Chlorine atom in it. While attempting to
performing a protein-ligand simulation, the Gromacs returns an error
message. It is observed that the
*CGenFF server *
Generate two additional lines, as shown below, in lig.str file

ATOM LP1    LPH     0.050 ! on Cl1
LONEPAIR COLI LP1    Cl1    C18    DIST 1.6400 SCAL 0.0

Which later add an additional line in ' lig.gro ' file generated using

python cgenff_charmm2gmx.py LIG lig_fix.mol2 lig.str charmm36-mar2019.ff
gmx editconf -f lig_ini.pdb -o lig.gro

at the later stages of simulation, the above 'LP1 lines' gives the
following error message
-----------------------------------------------------------------------------------------------------
WARNING 1 [file topol.top, line 60334]:
  You are using Ewald electrostatics in a system with net charge. This can
  lead to severe artifacts, such as ions moving into regions with low
  dielectric, due to the uniform background charge. We suggest to
  neutralize your system with counter ions, possibly in combination with a
  physiological salt concentration.
-------------------------------------------------------------------------------------------------------
How to over come this problem while performing a simulation with a ligand
containing halogens like Chlorine?

1) Delete Chlorine atom form the ligand molecule after an optimization with
Avogadro and before uploading to CGenFF Server ?
or
2) Delete  (ATOM LP1    LPH     0.050 ! on Cl1 and LONEPAIR COLI LP1    Cl1
   C18    DIST 1.6400 SCAL 0.0) lines from ' lig.str ' file before further
processing to ' lig.gro ' and later part of simulation can manage with
-maxwarn 1 ?
or
3) just delete LP1 line from lig,gro and in later part of the simulation
manage the lig.prm and lig.itp file?
or
4) Gromacs 2020.1 can effectively handle this ' LP1 ' ?
or
5) Any other methods to overcome the problem with Halogens / lone pair