Rapid near-atomic resolution single-particle 3D reconstruction with SIMPLE

Cyril F. Reboul, Simon Kiesewetter, Michael Eager, Matthew Belousoff, Tiangang Cui, Hans De Sterck, Dominika Elmlund, Hans Elmlund

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)


Cryogenic electron microscopy (cryo-EM) and single-particle analysis enables determination of near-atomic resolution structures of biological molecules. However, large computational requirements limit throughput and rapid testing of new image processing tools. We developed PRIME, an algorithm part of the SIMPLE software suite, for determination of the relative 3D orientations of single-particle projection images. PRIME has primarily found use for generation of an initial ab initio 3D reconstruction. Here we show that the strategy behind PRIME, iterative estimation of per-particle orientation distributions with stochastic hill climbing, provides a competitive approach to near-atomic resolution single-particle 3D reconstruction. A number of mathematical techniques for accelerating the convergence rate are introduced, leading to a speedup of nearly two orders of magnitude. We benchmarked our developments on numerous publicly available data sets and conclude that near-atomic resolution ab initio 3D reconstructions can be obtained with SIMPLE in a matter of hours, using standard over-the-counter CPU workstations.

Original languageEnglish
Pages (from-to)172-181
Number of pages10
JournalJournal of Structural Biology
Issue number2
Publication statusPublished - Nov 2018


  • 3D reconstruction
  • cryo-EM
  • Electron microscopy
  • Image processing
  • Near-atomic resolution
  • Single-particle
  • Stochastic hill-climbing

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