Biophysical Assessment of Target Protein Quality in Structure‐Based Drug Discovery

Hennig Michael, Rufer Arne

Chapter 7 in: Structural Biology in Drug Discovery: Methods, Techniques and Practices, p. 143-164, 2020

Along the entire value creation chain of drug discovery, biophysical methods are used to reveal details on the molecular properties of a target protein and its complexes with endogenous and pharmaceutical ligands. The ultimate goal of biophysical characterization of proteins with respect to drug design is their crystallization and the subsequent elucidation of the three-dimensional structure of the target/drug complex at atomic resolution. This chapter provides the example of the monotopic membrane protein carnitine palmitoyl transferase 2 from rat (CPT-2), which was used in the course of a drug discovery program to implement methods for the characterization of protein/detergent complexes. Continuous advancement of dedicated analysis software makes analytical ultracentrifugation a promising method for the purpose of characterizing protein-protein interactions. The chapter also presents a case study on minimizing macro-inhomogeneity.