%0 Journal Article %A Seth D. Axen %A Xi-Ping Huang %A Elena L. Cáceres %A Leo Gendelev %A Bryan L. Roth %A Michael J. Keiser %T A simple representation of three-dimensional molecular structure %D 2017 %R 10.1101/136705 %J bioRxiv %P 136705 %X 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.AUPRCAUC of the Precision-Recall CurveAUROCAUC of the Receiver Operating Characteristic CurveE3FPExtended Three-Dimensional FingerPrintECFPExtended Connectivity FingerPrintNBNaive Bayes ClassifierNNArtificial Neural NetworkPRCPrecision-Recall CurveRFRandom ForestROCReceiver Operating Characteristic CurveSEASimilarity Ensemble ApproachSVMSupport Vector MachineTCTanimoto coefficient %U https://www.biorxiv.org/content/biorxiv/early/2017/05/11/136705.full.pdf