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README.md

Project Files and Scripts

All necessary files and scripts to reproduce the work in the E3FP paper are included here.

Setup

Be sure that both e3fp and e3fp_paper packages and all required and optional dependencies are installed. Then, set the path to this directory to the environmental variable $E3FP_PROJECT, the path to the E3FP package to the variable $E3FP_PACKAGE, and the path to the e3fp_paper repo to $E3FP_PAPER.

Summary

The sections are best understood when browsed in the following order:

  1. Conformer Generation: Before performing 3D fingerprinting, one must generate a conformer library. While a user may provide their own conformer library, here we provide instructions for generating a library according to the method in the paper.
  2. Parameter Optimization: E3FP has several tunable parameters, including the input conformer library. Here, we use Spearmint to optimize the parameter set using 5-fold cross-validation to determine the optimal parameters that produce high-performing fingerprints.
  3. Fingerprint Comparison: Compare E3FP and ECFP4 fingerprints with each other and with other 3D similarity approaches.
  4. Benchmark: Compare compute times of ECFP4, E3FP, and FastROCS.
  5. Cross-Validation: E3FP and ECFP4 fingerprints are generated, and k-fold cross-validation is applied to determine the performance of these fingerprints using various classifiers.
  6. PDB Enrichment: Enrich for actives in ChEMBL20 using PDB conformations.
  7. Experiment Prediction: Having optimized E3FP and assessed its performance relative to ECFP4 in silico, we here identify molecule-target pairs that are predicted by the Similarity Ensemble Approach (SEA) to bind with E3FP but not with ECFP4. A subset of these predictions were verified experimentally.
  8. Analysis and Figures: This section contains all scripts necessary to generate figures, tables, and statistics that appeared in the paper.

The additional data and scripts directories contain all data files and general purpose scripts needed to perform the analyses in these sections, except where otherwise noted.