ABL resistance

This repository will be used to benchmark and improve KinoML and Perses.

Ideas

• reproduce ABL:inhibitor structures from Hauser 2018 using the KinoML pipeline
• run mutation benchmark from Aldeghi 2019 using OpenFF 1.2.0
• absolute free energy calculations with Yank might be interesting too
• long simulations to analyze stability of a variety of ABL:inhibitor complexes
• dock ATP/Mg2+ in binding pocket and analyze the effect of point mutations
• scale up to KINOMEScan data

How to use this repository

1. Clone repository

git clone https://github.com/openkinome/abl_resistance

2. Create Conda environment

conda env create -f environment.yml
conda activate abl_resistance

Structure

• notebooks/atp_kinase_conformations.ipynb
  • jupyter notebook analyzing the conformations of ATP bound kinases
• notebooks/abl1_atp_modeling.ipynb
  • jupyter notebook generating an ABL1 ATP complex
• notebooks/abl_complex_modeling.ipynb
  • jupyter notebook generating inhibitor bound complexes for the Hauser 2018 benchmark
• notebooks/abl_complex_modeling_with_water.ipynb
  • jupyter notebook using updated KinoML functionalities to generate inhibitor bound complexes for the Hauser 2018 benchmark including water

Authors

• David Schaller [email protected]
• William Glass [email protected]

License

This repository is licensed under the MIT license.