Neural-Network Scoring Functions Identify Structurally Novel Estrogen-Receptor Ligands

J Chem Inf Model. 2015 Sep 28;55(9):1953-61. doi: 10.1021/acs.jcim.5b00241. Epub 2015 Sep 4.


The magnitude of the investment required to bring a drug to the market hinders medical progress, requiring hundreds of millions of dollars and years of research and development. Any innovation that improves the efficiency of the drug-discovery process has the potential to accelerate the delivery of new treatments to countless patients in need. "Virtual screening," wherein molecules are first tested in silico in order to prioritize compounds for subsequent experimental testing, is one such innovation. Although the traditional scoring functions used in virtual screens have proven useful, improved accuracy requires novel approaches. In the current work, we use the estrogen receptor to demonstrate that neural networks are adept at identifying structurally novel small molecules that bind to a selected drug target, ultimately allowing experimentalists to test fewer compounds in the earliest stages of lead identification while obtaining higher hit rates. We describe 39 novel estrogen-receptor ligands identified in silico with experimentally determined Ki values ranging from 460 nM to 20 μM, presented here for the first time.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Computer Simulation
  • Databases, Factual*
  • Drug Discovery*
  • Estradiol / chemistry
  • Humans
  • Ligands
  • Models, Biological
  • Molecular Conformation
  • Neural Networks, Computer*
  • Protein Binding
  • Receptors, Estrogen / antagonists & inhibitors
  • Receptors, Estrogen / chemistry*


  • Ligands
  • Receptors, Estrogen
  • Estradiol