Molecular Dynamics Simulation of ARSA
From Bioinformatikpedia
Preparation
To prepare the pdb-structure for the molecular dynamics simulation we did all steps mentioned in the task-description and also did 5 rounds of minimization with minimise. We chose two mutations that seem to be interesting:
- Mutation 7 (T409I) which is disease causing.
- Mutation 8 (N440S) which is neutral.
Both proteins showed the same pattern in the structure based mutation analysis: SCWRL predicted, that the H-bond pattern change. SCWRL and FoldX predict a stabilizing effect, while minimise predicts a destabilizing effect.
local preparation with gromacs
To prepare the structure for the long minimization-runs we wrote two scripts.
Script 1:
#!/bin/bash if [ -z "$1" ]; then echo usage: $0 [name of pdb file without .pdb] exit fi echo starting pdb2gmx pdb2gmx -f $1.pdb -o $1.gro -p $1.top -water tip3p -ff amber03 -vsite hydrogens > pdb2gmx.out wait echo finished pdb2gmx echo "######################################################################" echo editconf editconf -f $1.gro -o $1_box.gro -bt dodecahedron -d 1.0 > editconf.out wait echo finished editconf echo "######################################################################" echo genbox genbox -cp $1_box.gro -cs spc216.gro -p $1.top -o $1_water.gro > genbox.out wait echo finished genbox echo "######################################################################" echo grompp grompp -v -f $1_1.mdp -c $1_water.gro -p $1.top -o $1_water.tpr > grompp1.out wait echo finished grompp echo "######################################################################" echo genion genion -s $1_water.tpr -o $1_solv.pdb -conc 0.1 -neutral -pname NA+ -nname CL- > genion.out wait echo finished genion echo "######################################################################" echo Do now: echo - copy everything after the 13 into a new file echo - run get_changes with this new file echo - copy the old top file and make the changes you get from get_changes in the copy
At this point some manual work needs to be done. Then script 2 could be used:
#!/bin/bash if [ -z "$1" ]; then echo usage: $0 [name of pdb file without .pdb] exit fi echo grompp grompp -v -f $1_2.mdp -c $1_solv2.pdb -p $1.top -o $1_solv_min.tpr wait echo finished grompp echo "######################################################################" echo mdrun mdrun -v -deffnm $1_solv_min -c $1_solv_min.pdb wait echo finished mdrun echo "######################################################################" echo genrestr genrestr -f $1_solv_min.pdb -o $1.itp wait echo finished genrestr echo "######################################################################" echo grompp grompp -v -f $1_2.mdp -c $1_solv_min.pdb -p $1.top -o $1_solv_min2.tpr wait echo finished grompp echo "######################################################################" echo mdrun mdrun -v -deffnm $1_solv_min2 -c $1_solv_min2.pdb wait echo finished mdrun echo "######################################################################" echo grompp grompp -v -f nvt.mdp -c $1_solv_min2.pdb -p $1.top -o $1_nvt.tpr wait echo finished grompp echo "######################################################################" echo the first long mdrun mdrun -v -deffnm $1_nvt wait echo finished the first long mdrun echo "######################################################################" echo grompp grompp -v -f npt.mdp -c $1_nvt.gro -p $1.top -o $1_npt.tpr wait echo finished grompp echo "######################################################################" echo the second long mdrun mdrun -v -deffnm $1_npt wait echo finished the second long mdrun echo "######################################################################" echo "grompp to prepare for lrz" grompp -v -f md.mdp -c $1_npt.gro -p $1.top -o $1_md.tpr wait echo "finished grompp to prepare for lrz" echo "######################################################################"
LRZ-runs with gromacs
To run gromacs on the LRZ-cluster we used the following config-file: (TODO: include working config-file)