Step
For more info please visit
https://github.com/pritampanda15/Molecular-Dynamics/blob/master/CHARMM_scripts/CHARMM-GROMACS-LIGAND%20-%20insert%20molecules%20random
Step 1
Download molecule from PUBCHEM/ZINC or fetch using tools like wget or curl.
wget http://example.com/molecule.pdb
Step 2
Extract ligand from AutoDock vina results.
cut -c-66 XYZ_out_ligand_01 > ligand.pdb
Step 3
Combine receptor and ligand into a single complex file.
cat receptor.pdbqt ligand.pdb | grep -v '^END ' | grep -v '^END$' > complex.pdb
Step 4
Convert PDB to SYBYL mol2 format using Avogadro.
Open the molecule in Avogadro and save it as SYBYL mol2 format.
Step 5
Sort mol2 bonds for CGenFF using a Perl script.
perl sort_mol2_bonds.pl ligand.mol2 ligand_fix.mol2
Step 6
Upload ligand to CGenFF and generate .str files.
Use the CHARMM General Force Field (CGenFF) online tool to generate .str files.
Step 7
Modify ligand_fix.mol2 by replacing ***** with UNK/LIG/DRG.
Edit the @<TRIPOS>MOLECULE section in ligand_fix.mol2. (change it to UNK/LIG/DRG etc as per your convinience)
Step 8
Modify .str file for RESI, changing ***** to UNK/LIG/DRG.
Edit RESI ***** to RESI UNK/LIG/DRG in the .str file.
Step 9
Convert CHARMM to GROMACS format.
python cgenff_charmm2gmx.py LIG ligand_fix.mol2 ligand.str charmm36-feb2021.ff
Step 10
Copy CHARMM36 forcefield to your working directory.
Download CHARMM36-feb2021.ff from MacKerell's website.Remember to copy Charmm36-feb2021.ff forcefiled folder from MacKerell website.
Step 11
Convert PDB to GRO format.
gmx_mpi editconf -f unk_ini.pdb -o unk.gro
Step 12
Generate protein topology.
gmx pdb2gmx -f crystal.pdb -o processed.gro -missing -i posre.itp
Step 13
Generate position restraints.
gmx_mpi genrestr -f processed.gro -o crystal.itp
Step 14
Define position restraints in topology.
Edit topol.top to include POSRES_CRYSTAL using #ifdef and #include.
Step 15
Define the simulation box.
gmx_mpi editconf -f processed.gro -o newbox.gro -c -d 1.0 -bt cubic
Step 16
Solvate the system.
gmx_mpi solvate -cp newbox.gro -cs spc216.gro -o solv.gro -p topol.top
Step 17
Prepare for ion addition.
gmx_mpi grompp -f ions.mdp -c solv.gro -p topol.top -o ions.tpr
Step 18
Add ions to neutralize the system.
gmx_mpi genion -s ions.tpr -o solv_ions.gro -p topol.top -pname NA -nname CL -neutral
Step 19
Insert molecules (e.g., ligands) into the system.
gmx_mpi insert-molecules -f solv_ions.gro -ci unk.gro -replace -nmol 20
Step 20
Run energy minimization.
gmx_mpi grompp -f em.mdp -c out.gro -r out.gro -p topol.top -o em.tpr -maxwarn -1
Step 21
Start energy minimization.
mpprun gmx_mpi mdrun -v -deffnm em
Step 22
Create an index file for the UNK molecule.
gmx_mpi make_ndx -f unk.gro -o index_unk.ndx
Step 23
Create an index file for equilibration.
gmx_mpi make_ndx -f em.gro -o index.ndx
Step 24
Prepare the system for equilibration.
gmx_mpi grompp -f step4.1_equilibration.mdp -o equil.tpr -c em.gro -r out.gro -p topol.top -n index.ndx -maxwarn -1
Step 25
Run the equilibration process.
gmx_mpi mdrun -v -deffnm equil
Step 26
Prepare the system for the production run.
gmx_mpi grompp -f step5_production.mdp -o md.tpr -c equil.gro -p topol.top -n index.ndx -maxwarn -1
Step 27
Start the production run.
gmx_mpi mdrun -deffnm md
Step 28
Extend the simulation time.
gmx_mpi convert-tpr -s md_0_1.tpr -extend 100000 -o next.tpr
Step 29
Continue the simulation.
gmx_mpi mdrun -s next.tpr -deffnm md_0_1 -cpi md_0_1_prev.cpt