HOME

Step 4: Selection of the (enhanced sampled) configurations (HPC)

Once the batch jobs in Step 3 are finalized, we use the common tools of the GROMACS suite (trjconv) to extract the configurations of the target bound and unbound states generated by the HREM simulations on the HPC. To this end, for the bound state, we do:

  cd USER_SCRATCH/bound
  mkdir conf
  for i in {0..5}; do\
  echo "0" | gmx trjconv -f /BATTERY$i/scaled0/traj_comp.xtc -s /BATTERY$i/scaled0/HREM.tpr -pbc mol -ur  compact -b 2000 -skip 8 -sep -o conf/conf"$i"_.pdb\
  done

For the unbound state, we do:

  cd USER_SCRATCH/unbound
  mkdir conf
  for i in {0..3}; do\
  echo "0" | gmx trjconv -f BATTERY$i/scaled0/traj_comp.xtc -s BATTERY$i/scaled0/HREM.tpr -pbc mol -ur  compact -b 3000 -skip 5 -sep  -o conf/conf"$i"_.gro -box 3.00000 3.00000 3.00000 -center  
  done

These commands extract the target state configurations for the PF-07321332-3CL^pro complex generated in the Step 3 and store them (in gro format) in a conf directory. For the unbound state, prior to submission (Step 5), you need to execute the script addwater.sh(also provided in the SI.zip archive attached to the JCIM note) in the directory unbound. The script combines the HREM-sampled gas-phase configurations with a box of equilibrated water in standard conditions, generating a directory gro_lw containing the starting configurations for the NS unbound state ligand growth.

The generation of the starting configurations can also be done using simple scripts for the bound state and unbound state, available in the SI.zip attached to the JCIM paper.
Extraction of the HREM-generated configurations for the bound and unbound state requires few seconds.

N.B.(1): The printing frequency (and hence the number of decorrelated enhaced-sampled configurations in the target states) is specified in the HPC_Drug-generated mdp GROMACS input files for the HREM simulations, also available at the vDSSB Zenodo repository.
N.B(2): In addwater.sh the number 3072 and 3139 are relative to our example. 3072 is the number of atoms in the HPC_Drug provided equilibrated water box; 3139 is the total number of water+ligand atoms (3072+67 in our model).