Binding energy calculations by molecular mechanics–generalized Born surface area

The calculations of binding free energy were enabled by the python program MMPBSA.py that is included within AmberTools (v16). In this study, the standard single-trajectory protocol was considered for calculating the binding free energies of Arg1333 and Arg1335 to the recognized nucleotides (i.e. AG or GG dependent on the specific systems). The single-trajectory protocol extracts the structural "snapshots" from the same trajectory for the complex, receptor (here Arg1333 and Arg1335), and ligand (AG/GG). The detailed precedure to compute the binding free energy for each system is presented below.

1. use AmberTools cpptraj to obain a stripped receptor-ligand complex trajectory (e.g. traj_trimmed.dcd) from the original simulation trajectory with explicit water and ions.
2. use AmberTools parmed (or cpptraj or tleap) to obtain three respective .prmtop (Amber parameter and topology) files for the complex, receptor and ligand (e.g. COM.prmtop, REC.prmtop, LIG.prmtop). 
3. prepare a IN (e.g. mmgbsa.in) file for MMPBSA.py that specifies specific parameters and values. 
4. run MMPBSA.py 

mmgbsa.in: 

#######################################################

&general
 startframe=1,
 endframe=1000,
 interval=2,

 receptor_mask=":1-2",
 ligand_mask=":3-4",
 verbose=1,
 keep_files=1,
 netcdf=1,
 use_sander=0,
 entropy=0,
/

&gb
 igb=1,
 saltcon=0.150,
/
#######################################################

Below is a bash script for executing MMPBSA.py:

#######################################################

MMPBSA_CMD=$(which MMPBSA.py.MPI)
MMPBSA_IN="./mmgbsa.in"
MMPBSA_OUT="./FINAL_RESULTS_MMPBSA.dat"

COM_TOP="../prmtop/COM.prmtop"
REC_TOP="../prmtop/REC.prmtop"
LIG_TOP="../prmtop/LIG.prmtop"

TRAJ_LIST=$(ls ../traj_trimmed.dcd)

mpirun -np 10 ${MMPBSA_CMD} -O -i ${MMPBSA_IN} -o ${MMPBSA_OUT} -cp ${COM_TOP} -rp ${REC_TOP} -lp ${LIG_TOP} -y ${TRAJ_LIST}
#######################################################

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