Molecular modeling as a powerful technique for understanding small–large molecules interactions

In the present review we summarize recent work, aimed at a better understanding of the interactions in macromolecule–ligand complexes, performed by means of computational tools such as pseudoreceptor generation, molecular docking, conformational search and energy minimization. While the first approach has been applied when the three-dimensional structural properties of the biological target were unknown, the remaining protocols exploited the knowledge of the overall structure of the involved macromolecules and their active sites. Molecular modeling techniques were used in the cases reported to study and propose macromolecular binding sites and to predict their interactions with bioactive conformers of the ligands.