Editorial [Hot topic: Structure- and Ligand-Based Drug Design: Advances and Perspectives (Guest Editor: Adriano D. Andricopulo)]

Structure-based drug design (SBDD) and ligand-based drug design (LBDD) remain the most important strategies in drug discovery, covering a variety of current state of the art approaches. Both drug design technologies involve the integration of a number of independent sciences, providing efficient, effective, and challenging approaches to medicinal chemistry. In this special issue of Current Topics in Medicinal Chemistry, entitled Structure- and Ligand-Based Drug Design, six articles in the broad field of medicinal chemistry were included, with a particular focus on key drug design technologies that have a significant impact for the design and development of new chemical entities, such as: bioinformatics, cheminformatics, QSAR, molecular docking, molecular dynamics, pharmacophores, virtual screening, crystallography, NMR, and so on. Here are the highlights. Andricopulo, Salum & Abraham present a review of the current developments in structure-based virtual screening and receptor-based pharmacophores, highlighting achievements as well as challenges, along with the value of structure-based lead optimization. Examples are described in this review of the use of these modern methods for the identification and design of novel active compounds. Some of the lessons that have been learned about best practices in the application of these important drug design approaches are summarized. Bob Clark's review of the current state of prospective 3D QSAR starts by putting the field in context by way of a bibliographic survey of articles touching upon QSAR and docking in the Journal of Medicinal Chemistry over the last several years. It then provides a tabulation of prospective target- and ligand-based studies in the recent literature - i.e., those in which activity predictions were made and experimentally tested. A comparison of the performance of the various approaches - docking, pharmacophores, shape-based methods and molecular fields - indicates that mixed methods seem to generally be the most successful. Consideration of the common challenges faced by all of the approaches illuminates the roots of such synergies and suggests that combinations of docking with locally trained scoring systems hold particular promise for the future.