Advancements in macromolecular crystallography: from past to present

Protein Crystallography or Macromolecular Crystallography (MX) started as a new discipline of science with the pioneering work on the determination of the protein crystal structures by John Kendrew in 1958 and Max Perutz in 1960. The incredible achievements in MX are attributed to the development of advanced tools, methodologies, and automation in every aspect of the structure determination process, which have reduced the time required for solving protein structures from years to a few days, as evident from the tens of thousands of crystal structures of macromolecules available in PDB. The advent of brilliant synchrotron sources, fast detectors, and novel sample delivery methods has shifted the paradigm from static structures to understanding the dynamic picture of macromolecules; further propelled by X-ray Free Electron Lasers (XFELs) that explore the femtosecond regime. The revival of the Laue diffraction has also enabled the understanding of macromolecules through time-resolved crystallography. In this review, we present some of the astonishing method-related and technological advancements that have contributed to the progress of MX. Even with the rapid evolution of several methods for structure determination, the developments in MX will keep this technique relevant and it will continue to play a pivotal role in gaining unprecedented atomic-level details as well as revealing the dynamics of biological macromolecules. With many exciting developments awaiting in the upcoming years, MX has the potential to contribute significantly to the growth of modern biology by unraveling the mechanisms of complex biological processes as well as impacting the area of drug designing.