Predicting Drug-Target Interactions for New Drug Compounds Using a Weighted Nearest Neighbor Profile

PLoS One. 2013 Jun 26;8(6):e66952. doi: 10.1371/journal.pone.0066952. Print 2013.

Abstract

In silico discovery of interactions between drug compounds and target proteins is of core importance for improving the efficiency of the laborious and costly experimental determination of drug-target interaction. Drug-target interaction data are available for many classes of pharmaceutically useful target proteins including enzymes, ion channels, GPCRs and nuclear receptors. However, current drug-target interaction databases contain a small number of drug-target pairs which are experimentally validated interactions. In particular, for some drug compounds (or targets) there is no available interaction. This motivates the need for developing methods that predict interacting pairs with high accuracy also for these 'new' drug compounds (or targets). We show that a simple weighted nearest neighbor procedure is highly effective for this task. We integrate this procedure into a recent machine learning method for drug-target interaction we developed in previous work. Results of experiments indicate that the resulting method predicts true interactions with high accuracy also for new drug compounds and achieves results comparable or better than those of recent state-of-the-art algorithms. Software is publicly available at http://cs.ru.nl/~tvanlaarhoven/drugtarget2013/.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artificial Intelligence
  • Computational Biology / methods*
  • Drug Discovery / methods*
  • Molecular Targeted Therapy*
  • Pharmaceutical Preparations / metabolism*
  • Protein Binding
  • Proteins / metabolism*

Substances

  • Pharmaceutical Preparations
  • Proteins

Grants and funding

This work has been partially funded by the Netherlands Organization for Scientic Research (NWO) within the NWO project 612.066.927. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.