Fragment screening is an excellent method to predict protein druggability. The presentation will discuss the characteristics and advantages of fragment libraries that cover very broad chemical space, enabling high hit rates and the identification of unique binding pockets. Beyond the fragment screening itself, we will look at the importance of employing a full program, which starts with scientific consultation, includes detailed protein engineering, and continues with the comprehensive biophysical hit confirmation. X-ray crystallography or NMR can be used either for fragment screening directly or in later stages for structural hit validation. This structural information is then used for in silico methods and helps to proceed with fragment-to-hit development.

This presentation will look at advanced technologies available for the target-to-hit developmental stage of the drug discovery process. Successful solutions integrate multiple aspects, including target acquisition, hit identification, and comprehensive characterization of hit series, including a dissection of mechanism of action (MoA) by using state-of-the art structural biology approaches. With an ever-increasing number of challenging and often “first-in-the class” targets, we will examine the value of unique workflows ranging from protein engineering to screenings (fragment and DNA encoded library screenings) and beyond to accelerate the drug discovery process.