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

Ti Yen Lan, Jennifer L. Wierman, Mark W. Tate, Hugh T. Philipp, Jose M. Martin-Garcia, Lan Zhu, David Kissick, Petra Fromme, Robert F. Fischetti, Wei Liu, Veit Elser, Sol M. Gruner

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)548-558
Number of pages11
JournalIUCrJ
Volume5
DOIs
StatePublished - Jan 1 2018

Fingerprint

Microcrystals
Synchrotrons
Storage rings
microcrystals
synchrotrons
Diffraction
proteins
Proteins
Crystals
X-Rays
diffraction
X ray lasers
crystals
X rays
Crystallography
Free electron lasers
Radiation damage
Crystal orientation
x rays
radiation damage

Keywords

  • EMC algorithm
  • Protein microcrystallography
  • Sparse data
  • Storage-ring synchrotron sources
  • X-ray serial microcrystallography

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry
  • Materials Science(all)
  • Condensed Matter Physics

Cite this

Lan, T. Y., Wierman, J. L., Tate, M. W., Philipp, H. T., Martin-Garcia, J. M., Zhu, L., ... Gruner, S. M. (2018). Solving protein structure from sparse serial microcrystal diffraction data at a storage-ring synchrotron source. IUCrJ, 5, 548-558. https://doi.org/10.1107/S205225251800903X

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

In: IUCrJ, Vol. 5, 01.01.2018, p. 548-558.

Research output: Contribution to journalArticle

Lan, TY, Wierman, JL, Tate, MW, Philipp, HT, Martin-Garcia, JM, Zhu, L, Kissick, D, Fromme, P, Fischetti, RF, Liu, W, Elser, V & Gruner, SM 2018, 'Solving protein structure from sparse serial microcrystal diffraction data at a storage-ring synchrotron source', IUCrJ, vol. 5, pp. 548-558. https://doi.org/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. In: IUCrJ. 2018 ; Vol. 5. pp. 548-558.
@article{79e7d87cac78484eac4d759c6bb0d6f8,
title = "Solving protein structure from sparse serial microcrystal diffraction data at a storage-ring synchrotron source",
abstract = "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 {\AA} 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.",
keywords = "EMC algorithm, Protein microcrystallography, Sparse data, Storage-ring synchrotron sources, X-ray serial microcrystallography",
author = "Lan, {Ti Yen} and Wierman, {Jennifer L.} and Tate, {Mark W.} and Philipp, {Hugh T.} and Martin-Garcia, {Jose M.} and Lan Zhu and David Kissick and Petra Fromme and Fischetti, {Robert F.} and Wei Liu and Veit Elser and Gruner, {Sol M.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1107/S205225251800903X",
language = "English (US)",
volume = "5",
pages = "548--558",
journal = "IUCrJ",
issn = "2052-2525",
publisher = "International Union of Crystallography",

}

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.

PY - 2018/1/1

Y1 - 2018/1/1

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

UR - http://www.scopus.com/inward/record.url?scp=85053159147&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053159147&partnerID=8YFLogxK

U2 - 10.1107/S205225251800903X

DO - 10.1107/S205225251800903X

M3 - Article

VL - 5

SP - 548

EP - 558

JO - IUCrJ

JF - IUCrJ

SN - 2052-2525

ER -