High-throughput continuous rotation electron diffraction data acquisition<i>via</i>software automation

Cichocka, Magdalena Ola; Ångström, Jonas; Wang, Bin; Zou, Xiaodong; Smeets, Stef

doi:10.1107/s1600576718015145

Cited by 145 publications

(178 citation statements)

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“…Another potential benefit of MicroED compared to x-ray diffraction is the possibility to refine atomic charges, exploring the charged state of proteinligand binding interactions (Yonekura et al, 2015;Yonekura & Maki-Yonekura, 2016). We anticipate that with future hardware and software development optimized towards automated and high-throughput data collection and processing (Cichocka et al, 2018), MicroED can become even more competitive with the ease and speed of synchrotron data collection and fragment screening. Coupled with the potential to refine atomic charges, MicroED may reveal novel details of the underlying molecular mechanisms that mediate inhibitor binding.…”

Section: Discussionmentioning

confidence: 99%

Visualizing drug inhibitor binding interactions using microcrystal electron diffraction

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Coincon

et al. 2020

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Visualizing drug inhibitor binding interactions at the atomic level is important for both structure-based drug design and fragment-based screening methods. Rapid and uniform soaking with potentially less lattice defects make small macromolecular crystals attractive targets for studying ligand biding using 3D microcrystal electron diffraction (MicroED). However, so far no drug inhibitor binding interactions could unambiguously be resolved by electron diffraction. Here, we use MicroED to study the binding of a sulfonamide inhibitor to human carbonic anhydrase isoform II (HCA II). We show that MicroED data can efficiently be collected in-house on a conventional TEM from thin hydrated microcrystals after a brief soaking with the clinical drug inhibitor acetazolamide (AZM). The data are of high enough quality to unequivocally fit and resolve the inhibitor bound to the active site of the protein. We anticipate MicroED can play an important role in future drug discovery experiments, complementing existing methods in structural biology such as x-ray and neutron diffraction.

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Section: Discussionmentioning

confidence: 99%

Visualizing drug inhibitor binding interactions using microcrystal electron diffraction

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Fisher

Coincon

et al. 2020

Preprint

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“…It was unclear if these new peaks corresponded to those from the MOF structure or with impurities like titanium oxyhydroxides;soindexing and subsequent structure solution remained impossible.G iven the small size of the crystallites,e ven in COK-47 L ,and the ambiguity of the PXRD data, we opted to perform continuous rotation electron diffraction (cRED) to obtain astructural model for COK-47. [13,14] Because electrons interact more strongly than X-rays,they are more suitable for single-crystal diffraction experiments on nanocrystalline materials.F igure 1b shows the reconstructed 3D reciprocal lattice observed with cRED performed on as ingle COK-47 L crystallite.T he collected data could be indexed in the monoclinic space group C2/c (unit cell as refined to PXRD data: a = 6.224 ; b = 30.183 ; c = 7.333 , b = 106.1358 8).…”

Section: In Memory Of Professor C Lambertimentioning

confidence: 99%

A Titanium(IV)‐Based Metal–Organic Framework Featuring Defect‐Rich Ti‐O Sheets as an Oxidative Desulfurization Catalyst

et al. 2019

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While titanium-based metal-organic frameworks (MOFs) have been widely studied for their (photo)catalytic potential, only af ew Ti IV MOFs have been reported owing to the high reactivity of the employed titanium precursors.T he synthesis of COK-47 is now presented, the first Ti carboxylate MOF based on sheets of Ti IV O 6 octahedra, whichc an be synthesized with ar ange of different linkers.C OK-47 can be synthesized as an inherently defective nanoparticulate material, rendering it ah ighly efficient catalyst for the oxidation of thiophenes.I ts structure was determined by continuous rotation electron diffraction and studied in depth by X-rayt otal scattering, EXAFS,a nd solid-state NMR. Furthermore,i ts photoactivity was investigated by electron paramagnetic resonance and demonstrated by catalytic photodegradation of rhodamine 6G.Metal-organic frameworks (MOFs) are crystalline coordination polymers constructed through the directional bonding of metal ions and polydentate organic linkers,o ften forming porous networks.O ver the last decade,M OFs have increas-ingly been investigated because of their highly tunable porosity and large density of accessible metal sites,m aking them suitable for catalytic applications,g as separation, and storage. [1][2][3][4] However,d eveloping chemically and thermally robust materials remains challenging.This has fueled interest in using oxophilic Group 4e lements such as Zr IV and Ti IV , which tend to form stable structures based on their strong metal-carboxylate bonds.Inthis context, numerous Zr MOFs have been reported, [5] but only 15 Ti IV MOFs have been described to date,ofwhich 5inthe past year, even though Ti precursors are cheap,n on-toxic,a nd Ti MOFs tend to show good redox activity and photoactivity. [6][7][8] Them uch higher tendency of Ti IV to form ill-defined oxyhydroxides lies at the basis of this discrepancyand makes the synthesis of Ti MOFs extremely challenging. [9,10] Themajority of the Ti MOFs reported to date contain Ti À Oclusters as secondary building unit (SBU), but very recently afew chain-based Ti MOFs were reported:DGIST-1, Ti-TBP, and MIL-177-HT. [7,11,12] Thed imensionality of the SBU greatly influences MOF properties,a swas exemplified by photoconductivity measurements on the chain-based MIL-177-HT and its cluster-based counterpart, MIL-177-LT. The latter showed negligible conductivity whereas MIL-177-HT features similar conductivity as nano-sized TiO 2 ,w hich demonstrates the benefit of increasing the SBU dimensionality to achieve bulk oxide properties.Herein, we report an ew,p hotoactive,T i IV 4,4'-biphenyldicarboxylate (bpdc 2À )M OF,t ermed COK-47, featuring ac omplex layer of TiO 6 octahedra as 2D SBU.I nterestingly, acareful choice of synthetic conditions allows for control over particle morphology and defect content, making COK-47 S (S = small particle) ah ighly active catalyst, for example towards the oxidation of dibenzothiophene.S everal isoreticular analogues with for instance terephthalate or 2,2'-bipyridine-5,5'-dicarboxylate linkers we...

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“…[13] ADPs are known to act as a" fudge factor" for poor quality data. [13] ADPs are known to act as a" fudge factor" for poor quality data.…”

Section: Structure Determination Using Electron Diffraction Datamentioning

confidence: 99%

“…13 CMAS NMR spectra for a) SSZ-26 (red), isomer Iinthe solid state (blue) and in water (black), b) SSZ-27 (red), isomer III in the solid state (blue) and in water (black). c)13 CC PMAS-NMR(0.5 ms cross-polarization contact time) spectra for SSZ-26 and SSZ-27.…”

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SSZ‐27: A Small‐Pore Zeolite with Large Heart‐Shaped Cavities Determined by Using Multi‐crystal Electron Diffraction

et al. 2019

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The high-silica zeolite SSZ-27 was synthesized using one of the isomers of the organic structure-directing agent that is knowntoproduce the large-pore zeolite SSZ-26 (CON). The structure of the as-synthesized form was solved using multicrystal electron diffraction data. Data were collected on eighteen crystals,a nd to obtain ah igh-quality and complete data set for structure refinement, hierarchical cluster analysis was employed to select the data sets most suitable for merging. The framework structure of SSZ-27 can be described as acombination of two types of cavities,one of which is shaped like ah eart. The cavities are connected through shared 8-ring windows to create straight channels that are linked together in pairs to form ao ne-dimensional channel system. Once the framework structure was known, molecular modelling was used to find the best fitting isomer,and this,inturn, was isolated to improve the synthesis conditions for SSZ-27.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.

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High-throughput continuous rotation electron diffraction data acquisitionviasoftware automation

Abstract: A semi-automated routine for continuous rotation electron diffraction has been developed, enabling high-throughput data collection. Serial electron crystallography combined with a deep convolutional network are used to screen for suitable crystals.

Cited by 145 publications

References 40 publications

Visualizing drug inhibitor binding interactions using microcrystal electron diffraction

Visualizing drug inhibitor binding interactions using microcrystal electron diffraction

A Titanium(IV)‐Based Metal–Organic Framework Featuring Defect‐Rich Ti‐O Sheets as an Oxidative Desulfurization Catalyst

SSZ‐27: A Small‐Pore Zeolite with Large Heart‐Shaped Cavities Determined by Using Multi‐crystal Electron Diffraction

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