Virtual Darwinian Drug Design: QSAR inverse problem, virtual combinatorialchemistry, and computational screening

The generation of diversity and its further selection by an external system is a common mechanism for the evolution of the living species and for the current drug design methods. This assumption allows us to label the methods based on generation and selection of molecular diversity as "Darwinian" on es, and to distinguish them from the structure-based, structure-modulation approaches. An example of a Darwinian method is the inverse QSAR. It consis ts of the computational generation of candidate chemical structures and the ir selection according to a previously established QSAR model. New trends i n the field of combinatorial chemical syntheses comprise the concepts of vi rtual combinatorial synthesis and virtual or computational screening. Virtu al combinatorial synthesis, closely related to inverse QSAR, can be defined as the computational simulation of the generation of new chemical structur es by using a combinatorial strategy to generate a virtual library. Virtual screening is the selection of chemical structures having potential desirab le properties from a database or virtual library in order to be synthesized and assayed. This review is mainly focused on graph theoretical drug desig n approaches, but a survey with key references is provided that covers othe r simulation methods.