Structure-Based Virtual Screening for Drug Discovery: a Problem-Centric Review

Structure-based virtual screening (SBVS) has been widely applied in early-stage drug discovery. From a problem-centric perspective, we reviewed the recent advances and applications in SBVS with a special focus on docking-based virtual screening. We emphasized the researchers’ practical efforts in real projects by understanding the ligand-target binding interactions as a premise. We also highlighted the recent progress in developing target-biased scoring functions by optimizing current generic scoring functions toward certain target classes, as well as in developing novel ones by means of machine learning techniques

Methyl-Readers and Inhibitors

Due to their prevalent role in epigenetic gene regulation, methyllysine and methylarginine domain readers have emerged as potential drug targets for small-molecule intervention. Within this book chapter, the biological role and the associated development of potent small molecules inhibiting the protein-protein interaction of methyllysine readers (Tudor, malignant brain tumor, chromo-, and PHD domain) will be discussed. The druggability of these readers and thus their potential to serve as targets for small-molecule ligands will be evaluated critically. Those domains (PWWP, WD40, ankyrin repeats, and ADD domains) which are not yet targeted will be evaluated for their biological actions and eventual therapeutic implications. To sum up, a comprehensive review of the state of the art for all relevant methyl-readers and their inhibitors if present will be given from a medicinal chemistry standpoint of view