Rational Drug Design

Chiara Luise, Dina Robaa, Luise, Chiara, Robaa, Dina

Computer-based approaches represent a powerful tool which helps to identify and optimize lead structures in the process of drug discovery. Computer-aided drug design techniques (CADD) encompass a large variety of methods which are subdivided into structure-based (SBDD) and ligand-based drug design (LBDD) methods. Several approaches have been successfully used over the last three decades in different fields. Indeed also in the field of epigenetics, virtual screening (VS) studies and structure-based approaches have been applied to identify novel chemical modulators of epigenetic targets as well as to predict the binding mode of active ligands and to study the protein dynamics.In this chapter, an iterative VS approach using both SBDD and LBDD methods, which was successful in identifying Spindlin1 inhibitors, will be described. All protocol steps, starting from structure-based pharmacophore modeling, protein and database preparation along with docking and similarity search, will be explained in details.