Predicting drug–target interactions for new drug compounds using a weighted nearest neighbor profile

Twan van Laarhoven and Elena Marchiori
2013, PLoS ONE 8(6): e66952.


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


Changelog of source code

See also our 2011 paper on drug-target interactions, for an earlier version of the code and results.


The paper is available under the Create Commons Attribution license.


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