Introduction

This repository contains scripts and jupyter notebooks to generate and analyze $\beta$-lactamase variants as well as analyze their experimental characterization as was done in our recent bioRxiv submission (see citation below):

Download this repository and navigate to the root directory

git clone https://github.com/gauthierscience/beta-lac-protein-design.git
cd beta-lac-protein-design

Notes:

• Data are available in the analysis_scripts/data directory. Analysis on new data must conform to the same format. Output of the scripts can be viewed as images in the jupyter notebooks.
• Analysis scripts are all provided as jupyter notebooks in the analysis_scripts directory. Output of these scripts is shown as embedded in the jupyter notebook.
• There are no notable installation or run time committments for any of these scripts.
• All MATLAB scripts and data (multiple sequence alignment and model) that were used to generate the designs are available in potts_design_release.zip. Please see README.m in the zip file for examples of how to execute new design generation.

Demo / Run analysis scripts

1. Optional create a virtual environment for analysis:

python3 -m venv ~/env/betalacdesign
source ~/env/betalacdesign/bin/activate

2. Install dependencies

pip3 install --upgrade pip
pip3 install pandas
pip3 install biopython
pip3 install seaborn
pip3 install openpyxl
pip3 install scikit-learn
pip3 install https://github.com/debbiemarkslab/EVcouplings/archive/develop.zip
pip3 install jupyter
pip3 install lmfit
pip3 install "numpy<1.24"

3. Navigate to script directory, launch jupyter notebook and open any of the notebooks in the gui (ipynb files).

cd analysis_scripts
jupyter notebook

Citation:

Simultaneous Enhancement of Multiple Functional Properties Using Evolution-informed Protein Design. Benjamin Fram^#, Yang Su^*, Ian Truebridge^*, Adam J. Riesselman, John B. Ingraham, Alessandro Passera, Eve Napier, Nicole N. Thadani, Samuel Lim, Kristen Roberts, Gurleen Kaur, Michael A. Stiffler, Debora S. Marks, Christopher D. Bahl, Amir R. Khan, Chris Sander, Nicholas P. Gauthier^#, Nature Communications, accepted in principle, 2024

# Correspondence should be addressed to Benjamin Fram and Nicholas Gauthier

bioRxiv version available at https://doi.org/10.1101/2023.05.09.539914