A minimal view of single-particle imaging with X-ray lasers

Abstract

One contribution of 27 to a Discussion Meeting Issue 'Biology with free-electron X-ray lasers'. Subject Areas: computational biology, biophysicsKeywords: X-ray free-electron laser, coherent diffraction, single particle imaging, bioimaging The ability to serially interrogate single biomolecules with femtosecond X-ray pulses from free-electron lasers has ushered in the possibility of determining the three-dimensional structure of biomolecules without crystallization. However, the complexity of imaging a sample's structure from very many of its noisy and incomplete diffraction data can be daunting. In this review, we introduce a simple analogue of this imaging workflow, use it to describe a structure reconstruction algorithm based on the expectation maximization principle, and consider the effects of extraneous noise. Such a minimal model can aid experiment and algorithm design in future studies.

Dragonfly: an implementation of the expand–maximize–compress algorithm for single-particle imaging

“…The ability to deal with a known structured background, mentioned above, would also be valuable for experimental data: the user would be able to provide a measured 'background file' to the reconstruction code. There are also plans to incorporate single-particle reconstruction while learning and rejecting an initially unknown background (Loh, 2014).…”

Progress in structure recovery from low dose exposures: Mixed molecular adsorption, exploitation of symmetry and reconstruction from the minimum signal level

“…The unknown parameters comprise in the former rotations and translations and in the latter only rotations. Powerful statistical approaches have been developed in order to recover the structure even when the dose is not sufficient for a straightforward assignment of these parameters [22][23][24][25][26][27][28][29][30][31][32][33][34] .…”

The birth of a new field

“…It was immediately realized that the high spatial coherence provided new approaches to the phase problem, for both SPs (Loh [7], Ourmazd and co-workers [8], Martin [9], Schwander et al [16]) and nanocrystals (Millane & Chen [17], Kirian et al [18], Spence et al [19] and Barty et al [20]). Atomic resolution has so far been obtained from unknown structures only using nanocrystals (and near-atomic resolution in the FSS when small changes in a known structure are studied), so that a crucial area for development of the BioXFEL field is the development of new methods for growing nanocrystals (Kupitz et al [21], Caffrey et al [22], Gallat et al [23] and Stevenson et al [24]).…”

“…The machine, in a 2-mile-long tunnel near Stanford, generates 120 pulses of hard or soft X-rays per second, containing about 1 Â 10 12 photons per 10 fs pulse, and, using purpose-built detectors, allows the diffraction pattern from each pulse to be read-out and saved. Broadly, three types of experiments were first attempted-those in which hydrated protein nanocrystals were sprayed across the pulsed beam (serial femtosecond nanocrystallography, SFX), those in which the hard X-ray beam of micrometre dimensions traverses many biomolecules in a liquid jet (fast solution scattering, FSS-see contributions by Haldrup [4], Mendez et al [5] and Pande et al [6]), and single particle (SP) imaging, in which a beam of submicrometre dimensions scatters from an SP such as a virus [7][8][9]. Before long many other experimental arrangements had also been tried during this exciting first 4 years, including fixed samples scanned across the beam for the study of two-dimensional membrane protein crystals [10], time-resolved SFX [11] (see also Moffat [12]), and new types of sample delivery devices, such as those based on the lipid cubic phase [13,14] and on electrospraying [15].…”