prepmd

A utility to automatically prepare structures from the PDB for molecular dynamics simulation.

Features

• Automatically download structures, sequences and metadata from the PDB and UNIPROT
• Automatically fill missing loops with modeller
• Automatically add missing atoms and convert non-standard residues with pdbfixer
• Automatically propagate metadata through to finalised structure files
• Automatically resolve steric clashes and minimise structures
• A simple command-line interface for running molecular dynamics with OpenMM
• AIIDA integration

Installation

• Install Conda (if you don't already have it)
• Clone this repo and enter the folder: git clone git@github.com:HECBioSim/prepmd.git && cd prepmd
• Run conda env create --name prepmd --file environment.yaml && conda activate prepmd && pip install .
• For the modeller part of the workflow to work, you need to get a modeller license key and add it to modeller's config.py file. If you use conda, the key will be in envs/prepmd/lib/modeller-10.7/modlib/modeller/config.py relative to the path where conda is installed.

Preparing structures from the PDB for simulation

• A basic example: prepmd 6xov 6xov_processed.pdb will download the structure for PDB entry 6xov, process it and write it to 6xov_processed.pdb.
• If you already have a pdb file, you can instead run: prepmd --structure 6xov_input.pdb 6xov 6xov_processed.pdb. You still need to supply a PDB code, as the various file formats used by prepmd require one to be present.
• prepmd will attempt to guess the correct file formats from the filenames it's given. It won't perform implicit conversions, so make sure to start and end with the same file type.
• By default, prepmd will leave intermediate files in a randomly-named temporary directory. You can set the name of this directory: prepmd --wdir 6xov_temp 6xov 6xov.cif.
• By default, prepmd will read missing residues from the pdb/mmcif metadata, attempt to align the missing residues with the currently present residues, and then build missing loops. You can manually provide a FASTA file containing the alignment data with --fasta. You can also ask mdprep to get the sequence data from UNIPROT instead, with --download, though this is not recommended, as the raw sequence data can be very different from the PDB and cause the alignment to fail.
• Note: while both pdb and mmCif are supported, using the mmCif format is strongly recommended, as the pdb format has been deprecated since 2024.
• Use prepmd --help for a full list of parameters.

Running MD simulations

• runmd can run MD simulations using OpenMM.
• A basic example: runmd structure.cif --min_out structure_minimised.cif --traj_out traj.xtc --md_steps 5000 --step 100 will minimise and run a simulation of structure.cif, writing a trajectory to traj_out.xtc, for 5000 steps, saving one trajectory frame every 100 steps.
• If you already have a minimised structure, you can skip minimisation: runmd structure.cif --traj_out traj.xtc --md_steps 5000 --step 100 -nomin -notest
• Solvate the simulation box: runmd structure.cif -o structure_minimised.cif --traj_out traj.xtc --md_steps 500 --step 10 -solv tip4pew. tip3p, tip4pew and spce are supported. You can also add pressure coupling with --pressure 1.0 (for 1 bar)
• Run with different force fields: runmd structure.cif -o structure_minimised.cif --traj_out traj.xtc --md_steps 500 --step 50 -ff amber14 runs with amber14. AMOEBA is also available, and amber19 is available if you have a recent version of OpenMM.
• Finally, you may wish to fix the backbone in place and just equilibrate the side chains: runmd structure.cif -o structure_minimised.cif --fix_backbone -solv tip4pew --notest
• Use runmd --help for a full list of parameters.