TY - JOUR
T1 - Synchrotron radiation as a tool for macromolecular X-Ray Crystallography
T2 - A XXI century perspective
AU - Grabowski, Marek
AU - Cooper, David R.
AU - Brzezinski, Dariusz
AU - Macnar, Joanna M.
AU - Shabalin, Ivan G.
AU - Cymborowski, Marcin
AU - Otwinowski, Zbyszek
AU - Minor, Wladek
N1 - Funding Information:
We thank Alex Wlodawer, Zbyszek Dauter, Aina Cohen, Chloe Estrada and Chad Brautigam for their critical reading and discussions of the manuscript. This work was supported by the National Institute of General Medical Sciences grants R01-GM132595, R01-GM117080, R01-GM118619 and federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States Department of Health and Human Services under contract HHSN272201700060C. DB acknowledges the support of the Polish National Agency for Academic Exchange under Grant No. PPN/BEK/2018/1/00058/U/00001. We also thank Aina Cohen, Andrew Thompson, Pawel Grochulski, Marian Szebenyi, Manfred Weiss and Sarah Lee for providing valuable information about their facilities.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/2/15
Y1 - 2021/2/15
N2 - Intense X-rays available at powerful synchrotron beamlines provide macromolecular crystallographers with an incomparable tool for investigating biological phenomena on an atomic scale. The resulting insights into the mechanism's underlying biological processes have played an essential role and shaped biomedical sciences during the last 30 years, considered the “golden age” of structural biology. In this review, we analyze selected aspects of the impact of synchrotron radiation on structural biology. Synchrotron beamlines have been used to determine over 70% of all macromolecular structures deposited into the Protein Data Bank (PDB). These structures were deposited by over 13,000 different research groups. Interestingly, despite the impressive advances in synchrotron technologies, the median resolution of macromolecular structures determined using synchrotrons has remained constant throughout the last 30 years, at about 2 Å. Similarly, the median times from the data collection to the deposition and release have not changed significantly. We describe challenges to reproducibility related to recording all relevant data and metadata during the synchrotron experiments, including diffraction images. Finally, we discuss some of the recent opinions suggesting a diminishing importance of X-ray crystallography due to impressive advances in Cryo-EM and theoretical modeling. We believe that synchrotrons of the future will increasingly evolve towards a life science center model, where X-ray crystallography, Cryo-EM, other experimental and computational resources, and knowledge are encompassed within a versatile research facility. The recent response of crystallographers to the COVID-19 pandemic suggests that X-ray crystallography conducted at synchrotron beamlines will continue to play an essential role in structural biology and drug discovery for years to come.
AB - Intense X-rays available at powerful synchrotron beamlines provide macromolecular crystallographers with an incomparable tool for investigating biological phenomena on an atomic scale. The resulting insights into the mechanism's underlying biological processes have played an essential role and shaped biomedical sciences during the last 30 years, considered the “golden age” of structural biology. In this review, we analyze selected aspects of the impact of synchrotron radiation on structural biology. Synchrotron beamlines have been used to determine over 70% of all macromolecular structures deposited into the Protein Data Bank (PDB). These structures were deposited by over 13,000 different research groups. Interestingly, despite the impressive advances in synchrotron technologies, the median resolution of macromolecular structures determined using synchrotrons has remained constant throughout the last 30 years, at about 2 Å. Similarly, the median times from the data collection to the deposition and release have not changed significantly. We describe challenges to reproducibility related to recording all relevant data and metadata during the synchrotron experiments, including diffraction images. Finally, we discuss some of the recent opinions suggesting a diminishing importance of X-ray crystallography due to impressive advances in Cryo-EM and theoretical modeling. We believe that synchrotrons of the future will increasingly evolve towards a life science center model, where X-ray crystallography, Cryo-EM, other experimental and computational resources, and knowledge are encompassed within a versatile research facility. The recent response of crystallographers to the COVID-19 pandemic suggests that X-ray crystallography conducted at synchrotron beamlines will continue to play an essential role in structural biology and drug discovery for years to come.
KW - COVID-19
KW - Data management
KW - Databases
KW - Drug discovery
KW - Macromolecular crystallography
KW - Structural biology
KW - Synchrotron radiation
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U2 - 10.1016/j.nimb.2020.12.016
DO - 10.1016/j.nimb.2020.12.016
M3 - Article
C2 - 33603257
AN - SCOPUS:85098990077
SN - 0168-583X
VL - 489
SP - 30
EP - 40
JO - Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms
JF - Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms
ER -