Entryway analysis

The eNTRy rules are a series of guidelines that can increase small-molecule accumulation in gram-negative bacteria. A molecule is likely to accumulate if it contains few rotatable bonds, low three dimensionality, and an ionizable nitrogen.

The webapp entry-way was created to aid in the application of these guidelines by performing the necessary predictions of physiochemical properties. Although freely available at entry-way.org, these same calculations can be performed locally.

Dependencies

Entryway relies on OpenBabel and RDKit for handling chemical structures and conformer generation and NumPy for globularity calculations. These dependencies are most conveniently installed via Conda. The included environment.yml file makes this straightforward:

conda env create -f environment.yml
conda activate entry-cli-env

Alternatively, they can be installed individually:

wget https://repo.continuum.io/miniconda/Miniconda3-latest-Linux-x86_64.sh -O miniconda.sh;
bash miniconda.sh -b -p $HOME/miniconda
export PATH="$HOME/miniconda/bin:$PATH"
conda update
conda create -n entry-cli-env python=3.6 numpy -y
conda install -c rdkit rdkit=2019.03.4.0 -y
conda install -c openbabel openbabel=3.1.1 -y
conda activate entry-cli-env

Running calculations

Although other file formats will be implemented shortly, molecules can be submitted as SMILES strings for now.

This can be achieved through command line arguments:

# Ampicillin
python calc_props.py -s "O=C(O)[C@@H]2N3C(=O)[C@@H](NC(=O)[C@@H](c1ccccc1)N)[C@H]3SC2(C)C"

# Deoxynybomycin
python calc_props.py -s "CC(C1=CC(C(C)=CC(N2C)=O)=C2C3=C1N4CO3)=CC4=O"

Alternatively, a batch file can be provided that contains several molecules with SMILES and names. Results are reported as a csv file. The name of the output file is optional. If no output file is specified, then the base name of the batch file is used:

# The following will provide the same result
python calc_props.py -b tests/b-lactams.smi -o tests/b-lactam.csv
python calc_props.py -b tests/b-lactams.smi

Citing

Please cite our paper on the eNTRy rules:

Richter, M. F.; Drown, B. S.; Riley, A. P.; Garcia, A.; Shirai, T.; Svec, R. L.; Hergenrother, P. J. Nature 2017, 545, 299-304.