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.