NP-Scout: Machine Learning Approach for the Quantification and Visualization of the Natural Product-Likeness of Small Molecules
Center for Bioinformatics (ZBH), Department of Informatics, Faculty of Mathematics, Informatics and Natural Sciences, Universität Hamburg, 20146 Hamburg, Germany
Department of Chemistry, University of Bergen, 5007 Bergen, Norway
Computational Biology Unit (CBU), Department of Informatics, University of Bergen, 5008 Bergen, Norway
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(2), 43; https://doi.org/10.3390/biom9020043
Received: 4 December 2018 / Revised: 21 January 2019 / Accepted: 21 January 2019 / Published: 24 January 2019
(This article belongs to the Special Issue New Approaches for the Discovery of Pharmacologically-Active Natural Compounds)
Natural products (NPs) remain the most prolific resource for the development of small-molecule drugs. Here we report a new machine learning approach that allows the identification of natural products with high accuracy. The method also generates similarity maps, which highlight atoms that contribute significantly to the classification of small molecules as a natural product or synthetic molecule. The method can hence be utilized to (i) identify natural products in large molecular libraries, (ii) quantify the natural product-likeness of small molecules, and (iii) visualize atoms in small molecules that are characteristic of natural products or synthetic molecules. The models are based on random forest classifiers trained on data sets consisting of more than 265,000 to 322,000 natural products and synthetic molecules. Two-dimensional molecular descriptors, MACCS keys and Morgan2 fingerprints were explored. On an independent test set the models reached areas under the receiver operating characteristic curve (AUC) of 0.997 and Matthews correlation coefficients (MCCs) of 0.954 and higher. The method was further tested on data from the Dictionary of Natural Products, ChEMBL and other resources. The best-performing models are accessible as a free web service at http://npscout.zbh.uni-hamburg.de/npscout.