This repo is used to generate the Figures for the publication: Cooperative Free Energy: Induced Protein-Protein Interaction, Cooperative Solvation, and Ligand Conformation in Protein-Ligand-Protein Ternary Complexes
doi: acs.jctc.5c00736
Figure1, Figure2, and Figure S1 are generated from simulation.ipynb
Plots in Figure4 are generated from Analysis.ipynb
All inputs for amber simulations are stored in the "./systems" folder.
./systems/ALB_pdbds/ stores the pdb files for the proteins (PDBID_A.pdb and PDBID_B.pdb)
./systems/ALB_pdbs/special_residues/ stores the parameters for special residues CSO and SEP used in PDB 6nv2
./systems/ALB_pdbs/Lignads/ stores the parameter for the ligand using antechamber with GAFF2 and AM1-BCC charges
Topology and Initial structure preparations: running ./systems/ALB_pdbs/prepare.sh prepares all simulation with a fix size with 0.15M NaCl. The box size and salt concentration can be changed by modifying the python template files in ALB_pdbs/template/
Go to ./systems/ and run 'bash multi_md.sh' to get the trajectories
Input files MMPB(GB)/SA calculations are stored in ./systems/endpoint/
running /systems/endpoint/multi.sh can split the topology and trajectories into 7 parts, including A, B, L, AL, BL, AB, and ALB.
running ./systems/endpoint/mmpbsa/multi.sh calculates the MMPBSA energy of each state in each trajectories
running ./systems/endpoint/mmgbsa/multi.sh calculates the MMGBSA energy of each state in each trajectories
MMPB(GB)/SA with Nwat variant can be calculated in a similar manner but the trajectories and topologies are split using the function "split_with_n_water" function ./systems/prepare_functions.sh
The standard output files are too large (>6GB in total), only the transformed numpy format is stored in the repo.
EX:
split_with_n_water 10 ${Ae[$i_name]} ${Bs[$i_name]} ${Be[$i_name]} ${L[$i_name]} $path $name'_ALB_'$ENV $name"takes the closest 10 water molecules as part of protein A.