ePharmaLib: A Versatile Library of e-Pharmacophores to Address Small-Molecule (Poly-)Pharmacology

J Chem Inf Model. 2021 Jul 26;61(7):3659-3666. doi: 10.1021/acs.jcim.1c00135. Epub 2021 Jul 8.


Bioactive compounds oftentimes bind to several target proteins, thereby exhibiting polypharmacology. Experimentally determining these interactions is however laborious, and structure-based virtual screening (SBVS) of bioactive compounds could expedite drug discovery by prioritizing hits for experimental validation. Here, we present ePharmaLib, a library of 15,148 e-pharmacophores modeled from solved structures of pharmaceutically relevant protein-ligand complexes of the screening Protein Data Bank (sc-PDB). ePharmaLib can be used for target fishing of phenotypic hits, side effect predictions, drug repurposing, and scaffold hopping. In retrospective SBVS, a good balance was obtained between computational efficiency and predictive accuracy. As a proof of concept, we carried out prospective SBVS in conjunction with a photometric assay, which inferred that the mechanism of action of neopterin (an endogenous immunomodulator) putatively stems from its inhibition (IC50 = 18 μM) of the human purine nucleoside phosphorylase. This ready-to-use library is freely available at http://www.pharmbioinf.uni-freiburg.de/epharmalib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Protein
  • Drug Discovery*
  • Humans
  • Ligands
  • Polypharmacology*
  • Prospective Studies
  • Retrospective Studies


  • Ligands