README.md

Ensembler

Software pipeline for automating omics-scale protein modeling and simulation setup.

Online documentation

• Go to the official online documentation.
• Read a preprint of the paper on bioRxiv.
• See the example dataset from modeling all human tyrosine kinases.

Authors

• Daniel L. Parton | daniel.parton@choderalab.org
• John D. Chodera | john.chodera@choderalab.org
• Patrick B. Grinaway | patrick.grinaway@choderalab.org

Overview of pipeline

1. Retrieve protein target sequences and template structures.
2. Build models by mapping each target sequence onto every available template structure, using Modeller.
3. Filter out non-unique models (based on a RMSD cutoff).
4. Refine models with implicit solvent molecular dynamics simulation.
5. Refine models with explicit solvent molecular dynamics simulation.
6. (optional) Package and/or compress the final models, ready for transfer or for set-up on other platforms such as Folding@Home.

Installation

First go to the Modeller website and get a license key (registration required; free for academic non-profit institutions).

Save the key as an environment variable:

export KEY_MODELLER=XXX

Then, using conda (installs all dependencies except the optional dependency Rosetta):

conda config --add channels omnia
conda config --add channels salilab
conda install ensembler

From source:

git clone https://github.com/choderalab/ensembler.git
cd ensembler
python setup.py install

Dependencies

• OpenMM - https://simtk.org/home/openmm
• Modeller - http://salilab.org/modeller/
• mdtraj - http://mdtraj.org/
• MSMBuilder - http://msmbuilder.org/
• PDBFixer - https://github.com/pandegroup/pdbfixer
• BioPython
• NumPy
• lxml
• PyYAML
• docopt
• mock
• Optional:
  • Rosetta (optional, for template loop reconstruction) - https://www.rosettacommons.org/software
  • MPI4Py (allows many Ensembler functions to be run in parallel using MPI)
  • Pandas (required for certain analysis functions)
  • subprocess32 (if using Python 2)
  • PyMOL (optional, for model alignment/visualization) - http://www.pymol.org/

Recommended approach is to install using conda (https://store.continuum.io/cshop/anaconda/). This will install all dependencies except for the optional dependency Rosetta, which must be installed separately by the user.