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Title: Solving protein structure from sparse serial microcrystal diffraction data at a storage-ring synchrotron source

In recent years, the success of serial femtosecond crystallography and the paucity of beamtime at X-ray free-electron lasers have motivated the development of serial microcrystallography experiments at storage-ring synchrotron sources. However, especially at storage-ring sources, if a crystal is too small it will have suffered significant radiation damage before diffracting a sufficient number of X-rays into Bragg peaks for peak-indexing software to determine the crystal orientation. As a consequence, the data frames of small crystals often cannot be indexed and are discarded. Introduced here is a method based on the expand–maximize–compress (EMC) algorithm to solve protein structures, specifically from data frames for which indexing methods fail because too few X-rays are diffracted into Bragg peaks. The method is demonstrated on a real serial microcrystallography data set whose signals are too weak to be indexed by conventional methods. In spite of the daunting background scatter from the sample-delivery medium, it was still possible to solve the protein structure at 2.1 Å resolution. The ability of the EMC algorithm to analyze weak data frames will help to reduce sample consumption. Furthermore, it will also allow serial microcrystallography to be performed with crystals that are otherwise too small to be feasibly analyzed atmore » storage-ring sources.« less
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [2] ;  [3] ;  [2] ;  [3] ;  [2] ;  [1] ; ORCiD logo [1]
  1. Cornell Univ., Ithaca, NY (United States)
  2. Arizona State Univ., Tempe, AZ (United States)
  3. Argonne National Lab. (ANL), Argonne, IL (United States)
Publication Date:
Grant/Contract Number:
AC02-06CH11357
Type:
Accepted Manuscript
Journal Name:
IUCrJ
Additional Journal Information:
Journal Volume: 5; Journal Issue: 5; Journal ID: ISSN 2052-2525
Publisher:
International Union of Crystallography
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org:
National Institutes of Health (NIH), National Cancer Institute; National Institutes of Health (NIH), National Institute of General Medical Sciences; USDOE
Country of Publication:
United States
Language:
English
Subject:
77 NANOSCIENCE AND NANOTECHNOLOGY; X-ray serial microcrystallography; sparse data; EMC algorithm; protein microcrystallography; storage-ring synchrotron sources
OSTI Identifier:
1472125

Lan, Ti -Yen, Wierman, Jennifer L., Tate, Mark W., Philipp, Hugh T., Martin-Garcia, Jose M., Zhu, Lan, Kissick, David, Fromme, Petra, Fischetti, Robert F., Liu, Wei, Elser, Veit, and Gruner, Sol M.. Solving protein structure from sparse serial microcrystal diffraction data at a storage-ring synchrotron source. United States: N. p., Web. doi:10.1107/S205225251800903X.
Lan, Ti -Yen, Wierman, Jennifer L., Tate, Mark W., Philipp, Hugh T., Martin-Garcia, Jose M., Zhu, Lan, Kissick, David, Fromme, Petra, Fischetti, Robert F., Liu, Wei, Elser, Veit, & Gruner, Sol M.. Solving protein structure from sparse serial microcrystal diffraction data at a storage-ring synchrotron source. United States. doi:10.1107/S205225251800903X.
Lan, Ti -Yen, Wierman, Jennifer L., Tate, Mark W., Philipp, Hugh T., Martin-Garcia, Jose M., Zhu, Lan, Kissick, David, Fromme, Petra, Fischetti, Robert F., Liu, Wei, Elser, Veit, and Gruner, Sol M.. 2018. "Solving protein structure from sparse serial microcrystal diffraction data at a storage-ring synchrotron source". United States. doi:10.1107/S205225251800903X. https://www.osti.gov/servlets/purl/1472125.
@article{osti_1472125,
title = {Solving protein structure from sparse serial microcrystal diffraction data at a storage-ring synchrotron source},
author = {Lan, Ti -Yen and Wierman, Jennifer L. and Tate, Mark W. and Philipp, Hugh T. and Martin-Garcia, Jose M. and Zhu, Lan and Kissick, David and Fromme, Petra and Fischetti, Robert F. and Liu, Wei and Elser, Veit and Gruner, Sol M.},
abstractNote = {In recent years, the success of serial femtosecond crystallography and the paucity of beamtime at X-ray free-electron lasers have motivated the development of serial microcrystallography experiments at storage-ring synchrotron sources. However, especially at storage-ring sources, if a crystal is too small it will have suffered significant radiation damage before diffracting a sufficient number of X-rays into Bragg peaks for peak-indexing software to determine the crystal orientation. As a consequence, the data frames of small crystals often cannot be indexed and are discarded. Introduced here is a method based on the expand–maximize–compress (EMC) algorithm to solve protein structures, specifically from data frames for which indexing methods fail because too few X-rays are diffracted into Bragg peaks. The method is demonstrated on a real serial microcrystallography data set whose signals are too weak to be indexed by conventional methods. In spite of the daunting background scatter from the sample-delivery medium, it was still possible to solve the protein structure at 2.1 Å resolution. The ability of the EMC algorithm to analyze weak data frames will help to reduce sample consumption. Furthermore, it will also allow serial microcrystallography to be performed with crystals that are otherwise too small to be feasibly analyzed at storage-ring sources.},
doi = {10.1107/S205225251800903X},
journal = {IUCrJ},
number = 5,
volume = 5,
place = {United States},
year = {2018},
month = {7}
}

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