An iterative compound screening contest method for identifying target protein inhibitors using the tyrosine-protein kinase Yes

Sci Rep. 2017 Sep 20;7(1):12038. doi: 10.1038/s41598-017-10275-4.


We propose a new iterative screening contest method to identify target protein inhibitors. After conducting a compound screening contest in 2014, we report results acquired from a contest held in 2015 in this study. Our aims were to identify target enzyme inhibitors and to benchmark a variety of computer-aided drug discovery methods under identical experimental conditions. In both contests, we employed the tyrosine-protein kinase Yes as an example target protein. Participating groups virtually screened possible inhibitors from a library containing 2.4 million compounds. Compounds were ranked based on functional scores obtained using their respective methods, and the top 181 compounds from each group were selected. Our results from the 2015 contest show an improved hit rate when compared to results from the 2014 contest. In addition, we have successfully identified a statistically-warranted method for identifying target inhibitors. Quantitative analysis of the most successful method gave additional insights into important characteristics of the method used.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Discovery / methods*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • High-Throughput Screening Assays / methods*
  • Humans
  • Machine Learning
  • Molecular Structure
  • Protein Binding
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-yes / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-yes / metabolism
  • Reproducibility of Results
  • Structure-Activity Relationship


  • Enzyme Inhibitors
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-yes
  • YES1 protein, human