Structural Biology in Drug Discovery: Methods, Techniques, and Practices (Wiley, 2020)

Structure-based drug discovery exploits the knowledge of the three-dimensional framework of biological molecules to enhance the process and outcome of drug design and development. Scientists can utilize modern structural biology techniques to characterize new therapeutic targets and develop efficient new drugs. Over the last few years, there have been significant improvements and advances in the field, leading to faster and more effective drug development at the preclinical stage. Today, a number of drugs have been derived from structure-based design programs and scientists continue to discover breakthrough methods in this fast-growing field.

The book gathers contributions from expert practitioners in the field and is divided into four sections:

Part I: Overview, concepts, and approaches.

Part II: Tools, with a strong focus on experimental techniques.

Part III: Case studies of structure‐based discovery on important, established but still challenging therapeutic target families, as well as on monoclonal antibodies as an example of biotherapeutics.

Part IV: Some present‐day frontiers such as intrinsically disordered proteins, neglected diseases, or viral resistance, and promising techniques for the future (XFELs and cryo‐EM) that have recently experienced spectacular developments but are not yet ready to be used on a routine basis in drug discovery because of some remaining technical bottlenecks and issues such as throughput, access to high‐end equipments, and availability of experienced practitioners. However, progress in these fields is rapid and should be carefully monitored for drug discovery to benefit as soon as possible from the latest technological advances.

The combined chapters, by authors writing from the frontlines of structural biology and drug discovery, give readers a comprehensive resource that :

? presents the benefits, limitations, and potentiality of major techniques in the field such as X-ray crystallography, NMR, neutron crystallography, cryo-EM, mass spectrometry and other biophysical techniques, and computational structural biology,

? includes detailed chapters on druggability, allostery, complementary use of thermodynamic and kinetic information, and powerful approaches such as structural chemogenomics and fragment-based drug design,

? emphasizes the need for the in-depth biophysical characterization of protein targets as well as of therapeutic proteins, and for a thorough quality assessment of experimental structures,

? illustrates advances in the field of established therapeutic targets like kinases, serine proteinases, GPCRs, and epigenetic proteins, and of more challenging ones like protein-protein interactions and intrinsically disordered proteins.

I am very grateful to the many co-authors who did a great job, and I hope this book will communicate enthusiasm for the exciting current developments in the structural biology aspects of drug discovery, and that it will be useful to the community and to students.

https://onlinelibrary.wiley.com/doi/book/10.1002/9781118681121