Molecular Modeling Strategies in Drug Design, Development, and Discovery Targeting Proteases

This chapter explores the critical role of proteases in human metabolism and the survival of pathogenic organisms, emphasizing their significance as drug development targets due to their biological importance. It outlines the standard nomenclature proposed by Schechter and Berger for categorizing protease subsites and substrates, which aids in understanding protease specificity and guiding inhibitor design. Despite advancements in developing potent peptidic protease inhibitors, challenges related to pharmacokinetic properties have led researchers to employ various drug design techniques. The chapter specifically examines marketed drugs targeting proteases for three viral diseases and Type 2 diabetes, highlighting the importance of computational tools in drug discovery campaigns and showcasing diverse design strategies, mainly structure-based drug design (SBDD) of peptidomimetics and macrocyclic inhibitors.