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UmbrellaPipeline

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Umbrella Sampling Pipeline for PMF of Protein Ligand Unbinding

What it does and how it works

This package estimates the sterically least hindered protein ligand dissociation pathway, conducts umbrella sampling along this pathway and subsequently calculates the Potential of Mean Force (PMF) for the protein ligand unbinding. No alignement of the protein cavity or manually placing ligands necessary.

drawing

Path Finding

Using a modified version of the A* path finding algorithm, this tool takes a docked ligand as a starting point, and then finds (if existing) the sterically least hindreds way out of the protein cavity by following a simple best-first search algorihtm.

drawing

Sampling

All sampling is done using openmm. After a equilibration period, the ligand is then placed at evenly spaced positions along the dissociation pathway and umbrella sampling is conducted.

PMF Calculations

The trajectories are analysed and the PMF is calculated using pymbar.

drawing

How-To

Visit the Documentation.

Requirements

  • Python 3.7, 3.8, 3.9
  • pip
  • numpy
  • openmm
  • openmmtools
  • scipy
  • pymbar
  • matplotlib
  • plotly
  • gemmi

Installation

Either download the source code or clone the repository to the desired destination and run

python setup.py install

inside the downloaded folder. Make sure to install the needed dependencies first.

Maintainer

Copyright

Copyright (c) 2022, Niels Maeder

Acknowledgements

Project based on the Computational Molecular Science Python Cookiecutter version 1.6.

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