Getting the most out of PubChem for virtual screening

Abstract

Introduction: With the emergence of the 'big data' era, the biomedical research community has great interest in exploiting publicly available chemical information for drug discovery. PubChem is an example of public databases that provide a large amount of chemical information free of charge.

Areas covered: This article provides an overview of how PubChem's data, tools, and services can be used for virtual screening and reviews recent publications that discuss important aspects of exploiting PubChem for drug discovery.

Expert opinion: PubChem offers comprehensive chemical information useful for drug discovery. It also provides multiple programmatic access routes, which are essential to build automated virtual screening pipelines that exploit PubChem data. In addition, PubChemRDF allows users to download PubChem data and load them into a local computing facility, facilitating data integration between PubChem and other resources. PubChem resources have been used in many studies for developing bioactivity and toxicity prediction models, discovering polypharmacologic (multi-target) ligands, and identifying new macromolecule targets of compounds (for drug-repurposing or off-target side effect prediction). These studies demonstrate the usefulness of PubChem as a key resource for computer-aided drug discovery and related area.

Keywords: PubChem; biological assay; cheminformatics; computational toxicology; computer-aided drug discovery; data mining; database; polypharmacology; quantitative structure-activity relationship (QSAR); virtual screening.

Figure 1

Data organization in PubChem. Chemical information deposited by more than 400 data contributors is organized into three primary databases: Substance, Compound, and BioAssay.

Figure 2

Chemical Space covered by PubChem. Panel (a) shows the proportion of compounds that satisfies Lipinski’s rule of 5 (Ref. 50) and Congreve’s rule of 3 (Ref. 51). Panel (b) shows the proportion of compounds that satisfy all criteria of Lipinski’s rule of five (Ro5), and those that violate one, two, three, and four criteria of the rule of five (Ro5−1, Ro5−2, Ro5−3, and Ro5−4), respectively.

Figure 3

Distribution of tested, active, and inactive compounds in PubChem. Tested compounds are those tested in at least one assay experiment archived in PubChem. Active compounds are those which are declared as active in at least one assay in PubChem. Inactive compounds are those which are not declared as active in any assay in PubChem.