Abstract: A method of construction and selection of virtual libraries in combinatorial chemistry is described, comprising the steps of: preparing a three-dimensional structure of a target macromolecule (PROT); determining one or more receptor sites of the macromolecular target (PROT); creating a first virtual library (300) of compounds starting with at least one input library (100;200); calculating a plurality of molecular descriptors for each molecule of the first virtual library (300), generating a second virtual library (400) containing each molecule of the first library (100; 200; 50) and the values of the molecular descriptors; selecting a representative subset (500) of the second virtual library (400); calculating for each molecule belonging to the representative subset a value of a quantity (Edock) associated with the formation of a bond between the target macromolecule (PROT) and each molecule belonging to the representative subset (500); and obtaining by way of simulation through “Machine Learning” methods for