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UCBbind

UCBbind is a program for predicting binding affinities for protein-ligand pairs. The program implements two modules:

  1. Module Y (Transfer prediction module): Uses sequence alignment and Tanimoto similarity to select reference protein-ligand pairs and replicate their binding free energies.
  2. Module X (Deep learning module): Takes features extracted from protein sequences and ligand SMILES strings to predict binding affinities.

Authors

Justin Purnomo, Caitlin Kim, Kunyang Sun, Yingze Wang, and Teresa Head-Gordon

Getting Started

This environment can be built via: conda env create -f env.yml

Training

To train Module X, run python X_prep.py To train Module Y, run python Y_prep.py

Note: The trained Module X has already been provided. Module Y requires large .idx and .pkl files and the BindingDB dataset, which are not included in the repo due to size. You can download the cleaned BindingDB dataset here:

After downloading BindingDB.csv and placing in the datasets folder, you can train Module Y.

Prediction

Predictions can be run using python FEpred.py.

The script expects a CSV file with the following columns: Sequence, SMILES, and Value. These describe the protein sequence of the query, the ligand SMILES of the query, and the experimental binding free energy in positive kcal/mol.

The default test set used in FEpred.py is: `test_fp = 'datasets/PDBbind.csv'. Note that in Y_prep.py, rows in BindingDB that are present in the test set are filtered out for reproducibility. Users do not need to do this for normal predictions.

Binder v Nonbinder Classification Accuracy

To assess classification accuracy, you can run python classifier_statistics.py

This script calculates the binder v nonbinder classification accuracy based on a pIC50 threshold of 5 for the binding affinity.

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