Rule interpreter: a chemical language for structure-based screening

Abstract

A chemical language for definition and use of logical rules in screening of chemical databases is described. The rules are based on user-defined screens, which combine substructure matching with constraints on molecular descriptors, stereochemical configurations and mutual 3D placements of chemical groups. Screens are written in extended SMILES notation with the option to define variant chemical groups and constraints in a single entry. Rules are Boolean logic expressions comprised of screens and preceding rules. Arbitrary decision trees can be constructed by using nested and conditional statements referring to the rules defined. The language was used in a database-integrated QSAR expert system for aquatic toxicity, which exploits the concept of toxicochemical analogues. Another example of its usage addresses the prediction of androgen receptor binding affinity.