This repository contains the code and files that form the basis of the manuscript "IMERGE-FEP: Improving Relative Free Energy Calculation Convergence with Chemical Intermediates"
Use setup.py for creating the environment for the intermediate generation
pip install -e .
Optionally, install dependencies for similarity scoring:
conda install openeye::openeye-toolkits #requires licence
conda install conda-forge::lomap2
to run the rhfe gromacs scripts also install pmx, parmed, openff and openmm
pip install git+https://github.com/deGrootLab/pmx.git@develop
pip install ParmEd
conda install conda-forge::openff-toolkit
conda install -c conda-forge openmm
download the benchmark ligands from: https://github.com/JenkeScheen/fep_intermediate_generation/tree/master/ligands
gromacs version: gromacs/2022.1/gcc.8.4.0-cuda.11.7.1
The functionality and use of the intermediate generator is shown the jupyter notebook rgroup_enumeration.ipynb
Folders
- rgroupinterm - a tool for pairwise R-group enumeration and pruning for the automatic creation of intermediate molecules
- rhfe_gromacs - the code, input files and md files to run the free energy perturbations described in the manuscript
- rhfe_analysis - code for analysing FEP output
- data - raw data used as input
- supplemental information - sdf files & visualization of molecules from the perturbations that were run
- figures - code for manuscript figures
Files
- rgroup_enumeration.ipynb - documentation basic functionality enumerator
- eg5_case_study.ipynb - application of enumerator on cogeneric series
- perserving_chirality.ipynb - background on chiral information in RDkit
- jacs_intermediates.py - script to enumerate all intermediates of the jacs files (takes a while)
- calc_scores.py - calculates similarity scores of intermediates using the pruners (takes two days to run this for all intermediates in the jacs set)
For the tpr files used for running of the RHFE simulations in gromacs can be found in
