Documenting and harnessing the biological potential of molecules in Distributed Drug Discovery (D3) virtual catalogs

Chem Biol Drug Des. 2017 Nov;90(5):909-918. doi: 10.1111/cbdd.13012. Epub 2017 Jun 12.


Virtual molecular catalogs have limited utility if member compounds are (i) difficult to synthesize or (ii) unlikely to have biological activity. The Distributed Drug Discovery (D3) program addresses the synthesis challenge by providing scientists with a free virtual D3 catalog of 73,024 easy-to-synthesize N-acyl unnatural α-amino acids, their methyl esters, and primary amides. The remaining challenge is to document and exploit the bioactivity potential of these compounds. In the current work, a search process is described that retrospectively identifies all virtual D3 compounds classified as bioactive hits in PubChem-cataloged experimental assays. The results provide insight into the broad range of drug-target classes amenable to inhibition and/or agonism by D3-accessible molecules. To encourage computer-aided drug discovery centered on these compounds, a publicly available virtual database of D3 molecules prepared for use with popular computer docking programs is also presented.

Keywords: Distributed Drug Discovery (D3); in silico chemoinformatics; molecular modeling; peptidomimetic; small molecule diversity; structure-based drug design; synthetic methods; unnatural amino acid derivatives; virtual screening.

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Computer-Aided Design*
  • Databases, Pharmaceutical
  • Drug Design*
  • Drug Discovery / methods*
  • Esterification
  • Humans
  • Ligands
  • Molecular Docking Simulation
  • NIMA-Interacting Peptidylprolyl Isomerase / antagonists & inhibitors
  • Peptidomimetics / chemistry
  • Peptidomimetics / pharmacology*
  • Quantitative Structure-Activity Relationship
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Software


  • Amino Acids
  • Ligands
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptidomimetics
  • Small Molecule Libraries