[gmx-users] Error running simulations with the protein frozen

[Justin Lemkul]

On 3/25/16 9:42 PM, Nuo Wang wrote:
> Hi Gromacs admins,
>
> I am trying to run MD simulations of protein solvated in water. I want to
> completely freeze the protein at its crystal conformation and only sample
> the solvent degrees of freedom (for comparison with Poisson-Boltzmann
> calculations that only use the crystal structure). I tried to follow the
> typical minimization-equilibration-production procedure described here:
> http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/lysozyme/index.html
>
> But I get this error at the energy minimization step:
> "Fatal error:
> step 11: Water molecule starting at atom 60322 can not be settled.
> Check for bad contacts and/or reduce the timestep if appropriate."
>
> If I take away the freeze protein commands in my minimize.mdp, then no
> error occurs:
> freezegrps    = Protein
> freezedim     = Y Y Y
>
> I checked my atom 60322, it is next to the protein, but it is neither
> clashing with anyone nor moving rapidly in my trajectory. Reducing timestep
> by 1000 times won't help either, error just occurs at a later step.
>
> I wonder how can I resolve this problem?

Freezing is a severe perturbation on the system, and taking a protein out of its 
crystal environment, dunking it in water, and expecting that conformation to be 
happy (or even sensible) is a bad assumption.  If you want to preserve the 
overall conformation, try something gentler like normal position restraints.

-Justin

> The script that I used is shown here, the input files in the script are
> linked below:
> ### Generate topology
> echo 9  | gmx pdb2gmx -f complex.pdb -o complex.gro -p complex.top -merge
> all -ignh -water tip3p
> ### Generate box information
>            gmx editconf -f complex.gro -o complex_newbox.gro -bt cubic -c
> -box 11 11 11
> ### Add water
>            gmx solvate -cp complex_newbox.gro -cs spc216.gro -o
> complex_solvated.gro -p complex.top
> ### Prepare ion parameters
>            gmx grompp -f ions.mdp -c complex_solvated.gro -p complex.top -o
> ions.tpr
> ### Add ions
> echo 13 | gmx genion -s ions.tpr -o complex_solvated_ions.gro -p
> complex.top -pname NA -nname CL -neutral -conc 0
> ### Generate index file
> echo q  | gmx make_ndx -f complex_solvated_ions.gro -o index.ndx
> ### Preparation for energy minimization for the non-protein atoms
>            gmx grompp -f minimize.mdp -c complex_solvated_ions.gro -n
> index.ndx -p complex.top -o em.tpr
> ### Energy minimization for the non-protein atoms
>            gmx mdrun -v -deffnm em -nt 1
>
> complex.pdb:
> https://drive.google.com/file/d/0B8oskrjCa2EMQURKd0J5bXdNRk0/view?usp=sharing
> ions.mdp:
> https://drive.google.com/file/d/0B8oskrjCa2EMS3M4cTdkRXRTRE0/view?usp=sharing
> minimize.mdp:
> https://drive.google.com/file/d/0B8oskrjCa2EMU0hZT0lxXzZuM1U/view?usp=sharing
>
> Thanks a lot!
> Nuo
>

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==================================================