Molecular Similarity Concepts for Informatics Applications.

The assessment of small molecule similarity is a central task in chemoinformatics and medicinal chemistry. A variety of molecular representations and metrics are applied to computationally evaluate and quantify molecular similarity. A critically important aspect of molecular similarity analysis in chemoinformatics and pharmaceutical research is that one is typically not interested in quantifying the degree of structural or chemical similarity between compounds per se, but rather in extrapolating from molecular similarity to property similarity. In other words, one assumes that there is a correlation between calculated similarity and specific properties of small molecules including, first and foremost, biological activities. Although similarity is a priori a subjective concept, and difficult to quantify, it must computationally be assessed in a formally consistent manner. Otherwise, there is little utility of similarity calculations. Consistent treatment requires approximations to be made and the consideration of alternative computational similarity concepts, as discussed herein.