2026/05/20 by Jill Chrencik, Hua-Poo Su, Yacob Gómez Llorente +42 · 1 voice
Materials Science · Biochemistry, Genetics and Molecular Biology · Medicine · #Enzyme Structure and Function #Advanced Electron Microscopy Techniques and Applications #Monoclonal and Polyclonal Antibodies Research
paper · doi:10.1107/s2059798326004390
openalex publication_date 2026/05/20 · openalex created_date 2026/05/27 · openalex updated_date 2026/07/23
Structural biology has fundamentally influenced pharmaceutical research and development at Merck Sharp & Dohme LLC, Rahway, New Jersey, USA, progressing from pioneering macromolecular crystallography in the 1980s to a fully integrated platform that today encompasses X-ray crystallography, cryo-electron microscopy, micro-electron diffraction and cryo-electron tomography. In this review, we present a comprehensive overview of how these complementary methods have advanced drug discovery across diverse therapeutic areas. We illustrate how atomic to cellular structural insights inform drug discovery and development, from target identification and validation, hit finding, lead identification through lead optimization and clinical progression. Furthermore, we describe how structural biology techniques aid in formulation strategies of antibodies and vaccines. Finally, we highlight the growing integration of ex situ and in situ approaches as a paradigm shift towards elucidating drug mechanisms in native cellular contexts, a transition poised to accelerate the discovery and development of next-generation therapeutics.