@article {Axen136705, author = {Seth D. Axen and Xi-Ping Huang and Elena L. C{\'a}ceres and Leo Gendelev and Bryan L. Roth and Michael J. Keiser}, title = {A simple representation of three-dimensional molecular structure}, elocation-id = {136705}, year = {2017}, doi = {10.1101/136705}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Statistical and machine learning approaches predict drug-to-target relationships from 2D small-molecule topology patterns. One might expect 3D information to improve these calculations. Here we apply the logic of the Extended Connectivity FingerPrint (ECFP) to develop a rapid, alignment-invariant 3D representation of molecular conformers, the Extended Three-Dimensional FingerPrint (E3FP). By integrating E3FP with the Similarity Ensemble Approach (SEA), we achieve higher precision-recall performance relative to SEA with ECFP on ChEMBL20, and equivalent receiver operating characteristic performance. We identify classes of molecules for which E3FP is a better predictor of similarity in bioactivity than is ECFP. Finally, we report novel drug-to-target binding predictions inaccessible by 2D fingerprints and confirm three of them experimentally with ligand efficiencies from 0.442 - 0.637 kcal/mol/heavy atom.}, URL = {https://www.biorxiv.org/content/early/2017/05/13/136705}, eprint = {https://www.biorxiv.org/content/early/2017/05/13/136705.full.pdf}, journal = {bioRxiv} }