TY - JOUR
T1 - Solving protein structure from sparse serial microcrystal diffraction data at a storage-ring synchrotron source
AU - Lan, Ti Yen
AU - Wierman, Jennifer L.
AU - Tate, Mark W.
AU - Philipp, Hugh T.
AU - Martin-Garcia, Jose M.
AU - Zhu, Lan
AU - Kissick, David
AU - Fromme, Petra
AU - Fischetti, Robert F.
AU - Liu, Wei
AU - Elser, Veit
AU - Gruner, Sol M.
N1 - Funding Information:
Veit Elser and Ti-Yen Lan received support from the US Department of Energy (DOE) (grant No. DE-SC0005827). Ti-Yen Lan was also supported by the Taiwan Government through a Scholarship to Study Abroad. CHESS is supported by the National Science Foundation (award No. DMR-1332208) and the MacCHESS resource is supported by the National Institute of General Medical Sciences (award No. GM-103485). Sol M. Gruner, Hugh T. Philipp and Mark W. Tate received support from the DOE (grant No. DESC0017631). Petra Fromme and Jose M. Martin-Garcia received support from the Center for Applied Structural Discovery (CASD) at the Biodesign Institute at Arizona State University, the Flinn Foundation Seed Grant (No. 1991), and the STC Program of the National Science Foundation through BioXFEL (No. 1231306). Lan Zhu and Wei Liu received support from the NIH (grant Nos. R21 DA042298 and R01 GM124152), the NSF STC (award No. 1231306) and the Flinn Foundation Seed Grant. This research used resources of the Advanced Photon Source, a US DOE Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.
PY - 2018
Y1 - 2018
N2 - 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. It will also allow serial microcrystallography to be performed with crystals that are otherwise too small to be feasibly analyzed at storage-ring sources.
AB - 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. It will also allow serial microcrystallography to be performed with crystals that are otherwise too small to be feasibly analyzed at storage-ring sources.
KW - EMC algorithm
KW - Protein microcrystallography
KW - Sparse data
KW - Storage-ring synchrotron sources
KW - X-ray serial microcrystallography
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U2 - 10.1107/S205225251800903X
DO - 10.1107/S205225251800903X
M3 - Article
AN - SCOPUS:85053159147
VL - 5
SP - 548
EP - 558
JO - IUCrJ
JF - IUCrJ
SN - 2052-2525
ER -