OSMES

Pipeline in python to perform One Substrate-Many Enzymes Screening (OSMES) of a substrate molecule bound to a PLP cofactor (external aldimine) against a library of PLP-dependent enzyme structures

Installation

Requirements

OS Requirements

The package development version is tested on Linux operating systems.

Software Requirements

Any version of micromamba >1.0
Packages requirement are listed in the env file

Hardware Requirements

10 cores, 10 Gb RAM

Cloning git repository

git clone https://github.com/lab83bio/OSMES.git
cd OSMES

Installation of ADFRsuite_x86_64Linux_1.096

wget https://ccsb.scripps.edu/adfr/download/1038/ -O 'adfr.tar.gz'
tar zxvf adfr.tar.gz 
cd ADFRsuite_x86_64Linux_1.0/
chmod +x install.sh
yes|bash install.sh -d ../ADFRsuite-1.0 -c 0 &>../ADFR_install.log
cd ..

Installation time: ~5 min

Create and activate mamba environment

micromamba create -f OSMES_explicit_env.txt -n OSMES -y
micromamba activate OSMES

Usage

Input files

OSMES pipeline required the following input files:

• substrate.pdbqt for ADFR
• substrate.txt for calculation of the catalytic favourable conformations (CFC)
• Enzyme set in pdb format
• coords.tsv with the specified coordinates of the gridbox center for each active site.

To produce the indicated input files, please use the OSMES.ipynb Colab Notebook and follow the instructions of the cells.

Running OSMES

make executable the file

chmod +x OSMES_submit.py

and then run the pipeline with the configuration file using the test dataset.

OSMES_submit.py OSMES.config

where in OSMES config are defined all the path and the parameters required by the analysis, an example below:

[PATHS]
# Specific input/output files
adfr_path = ADFRsuite-1.0/bin
Ligand = test/HTL_PLP.pdbqt # substrate file
reactions_file = test/HTL_PLP.txt # file with the atoms for the catalyitic favourable conformations and the gridbox sizes
receptor_dir = test/Mus_musculus/ # path to enzyme pdb files
coord_file = test/Mus_musculus/Mus_musuclus_coord.csv # coordinates file for every active site consdered in the enzymes set with specified center of the gridbox
outdir = test/OSMES_results # directory of results

[GPF]
spacing=0.375 
pocketMode = all

[DPF]
maxEvals = 5000000
nbRuns = 20
maxCores = 0 # Set 0 to use all cores available
clusteringRMSDCutoff = 3
popSize = 300

[OTHER]
imgFormat = pdf
flex_lysine = True # keep catalytic lysine as flexible receptor.

Expected output for the test set is in test/OSMES_results directory
Expected runtime ~30 min