Practical Cheminformatics

In a recent paper in the Journal of Medicinal Chemistry, Lewis Pennington, Ingo Muegge, and coworkers at Alkermes present an overview of Positional Analogue Scanning (PAS), a widely used technique in Medicinal Chemistry.  This is a simple, yet powerful, technique where one "walks" a particular substituent around the structure of a lead molecule and explores a variety of substitutions.   As an example, consider the case below from the paper where each aromatic "cH" is sequentially replaced with nitrogen. As Pennington and coworkers point out, these small changes can often have profound effects on the properties, metabolism, and biological activity of a molecule.  In addition to being able to generate ideas for new molecules, PAS  can be a powerful tool for computational chemists.  By generating a set of positional analogs, one can rapidly investigate how structural changes impact computed properties.  This information can be used to understand SAR and prioritize

In a preprint posted on bioRxiv on April 5, 2020, Franck Touret and coworkers from Aix Marseille Université published the results from a SARS-CoV-2 cellular assay of 1520 compounds from the Prestwick Chemical Library, a collection of off-patent marketed drugs.  Unfortunately, the authors published the preprint without including the chemical structures of the compounds.   Fortunately, Brian Cole used a couple of databases to associate structures with this screening data and posted the revised data, as well as the scripts he used to do the annotation on GitHub .  This short post serves two purposes.  It highlights data that may be useful to those working on treatments for SARS-CoV-2.  It may be possible to associate this screening data with recently released biophysical data and obtain mechanistic insights.  The solution that Brian came up with is generally applicable,  and can be applied to the many cases where data is published without associated chemical structures. In Bri