Small molecule superposition: A comprehensive overview on pose scoring of the latest methods

Abstract The superposition of small molecules is a standard technique in molecular modeling and for some more advanced in silico applications of drug discovery a critical prerequisite. The aims of superposing molecules are manifold. An assessment of the 3D similarity, an understanding of the SAR in a compound series, or ultimately an estimate of the likelihood of a compound to be active and selective against a target protein of interest. Considering so many objectives it is not surprising that new superpositioning methods are continuously developed and the overlay problem cannot be considered solved. We present 51 superposition methods with a focus on those published in the 21st century. For 36 methods that are currently available, we briefly describe and compare the respective pose generation and scoring processes. While the modeling community got a wealth of methods at hand, the scientific necessity of rigorous and comparable benchmarking becomes apparent. This article is categorized under: Data Science > Chemoinformatics Software > Molecular Modeling