Prediction of protein–protein complexes using replica exchange with repulsive scaling
Till Siebenmorgen till.siebenmorgen@tum.de, Michael Engelhard, Martin Zacharias
https://doi.org/10.1002/jcc.26187
Efficient Refinement and Free Energy Scoring of Predicted Protein–Protein Complexes Using Replica Exchange with Repulsive Scaling
Till Siebenmorgen, Martin Zacharias
https://doi.org/10.1021/acs.jcim.0c00853
Scripts are written in python 2.7 (for Amber users)
Following these steps you can set up a RS-REMD simulation
Perform a setup of the groupfile, modify the Lennard-Jones parameters and start the simulation:
python prepare_files_rs.py
python lj.py parm.top 4 -d 0.00 0.1 0.2 0.5 -e 1.00 0.95 0.90 0.80 -c heated.rst -r :1-66 -l :67-123 -hMassRepartitioning -o system.top | tee lj.log
source rs.run
lj.py (python lj.py -help):
parm.top = input topology file that you have created in advance of your system
4 = Number of replicas that you want to use, in our case 4; for proper systems between 8 and 16
-d = distance parameter for LJ scaling of the individual replica; for my systems with 16 replicas: -d 0.00 0.01 0.02 0.04 0.08 0.12 0.16 0.20 0.24 0.28 0.32 0.38 0.44 0.50 0.58 0.68
-e = epsilon parameter for LJ scaling of the individual replica; for my systems with 16 replicas: -e 1.00 0.99 0.98 0.97 0.96 0.94 0.92 0.90 0.88 0.86 0.84 0.82 0.80 0.78 0.76 0.74
-c = heated restart file
-r = receptor mask, specifies the receptor residues whose interaction should be scaled
-l = ligand mask, specifies the receptor residues whose interaction should be scaled
-hMassRepartitioning = if specified performs hMassRepartitioning on the topology files
-o = outputfile name of the generated replicas
From generated trajectories we can now calculate free energy differences. The simulations were performed in explicit solvent and the water molecues were stripped.
python reevaluate_trajs_for_biases.py
python mbar_freeEnergies.py
You might be able to use your python installation from ambertools. You can also install the necessary packages using anaconda
conda install -c conda-forge mdtraj
conda install -c ambermd ambertools
For the pymbar installation (in order to calculate free energies) you can use
pip install pymbar