TY - JOUR T1 - A simple representation of three-dimensional molecular structure JF - bioRxiv DO - 10.1101/136705 SP - 136705 AU - Seth D. Axen AU - Xi-Ping Huang AU - Elena L. Cáceres AU - Leo Gendelev AU - Bryan L. Roth AU - Michael J. Keiser Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/05/13/136705.abstract N2 - 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. ER -