<scp>DIALS</scp> as a toolkit

Winter, Graeme; Beilsten-Edmands, James; Devenish, N. E.; Gerstel, Markus; Gildea, Richard J.; McDonagh, David; Pascal, Elena; Waterman, David; Williams, Benjamin H.; Evans, Gwyndaf

doi:10.1002/pro.4224

Cited by 78 publications

(45 citation statements)

References 37 publications

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“…Diffraction data were collected on beamline I0-3 at the Diamond Light Source at 100 K using a wavelength of 0.9762 Å. Data were processed using Dials 97 via Xia2 98 and Aimless 99 within CCP4i2. 100 The datasets were phased using Molrep 101 and the M pro apo structure (PDB ID: 6YB7).…”

Section: Methodsmentioning

confidence: 99%

Penicillin Derivatives Inhibit the SARS-CoV-2 Main Protease by Reaction with Its Nucleophilic Cysteine

et al. 2022

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The SARS-CoV-2 main protease (M pro ) is a medicinal chemistry target for COVID-19 treatment. Given the clinical efficacy of β-lactams as inhibitors of bacterial nucleophilic enzymes, they are of interest as inhibitors of viral nucleophilic serine and cysteine proteases. We describe the synthesis of penicillin derivatives which are potent M pro inhibitors and investigate their mechanism of inhibition using mass spectrometric and crystallographic analyses. The results suggest that β-lactams have considerable potential as M pro inhibitors via a mechanism involving reaction with the nucleophilic cysteine to form a stable acyl–enzyme complex as shown by crystallographic analysis. The results highlight the potential for inhibition of viral proteases employing nucleophilic catalysis by β-lactams and related acylating agents.

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Section: Methodsmentioning

confidence: 99%

Penicillin Derivatives Inhibit the SARS-CoV-2 Main Protease by Reaction with Its Nucleophilic Cysteine

et al. 2022

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“…After symmetry determination, an overall best estimate of the unit cell is obtained by refinement of the unit cell parameters against the observed 2 θ angles, using the program (Winter et al ., 2021). This program minimises the unit cell constants against the difference between observed and calculated 2 θ values, which are determined from background-subtracted integrated centroids.…”

Section: Methodsmentioning

confidence: 99%

xia2.multiplex: a multi-crystal data analysis pipeline

Gildea¹,

Beilsten-Edmands²,

Axford³

et al. 2022

Preprint

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In macromolecular crystallography radiation damage limits the amount of data that can be collected from a single crystal. It is often necessary to merge data sets from multiple crystals, for example small-wedge data collections on micro-crystals, in situ room-temperature data collections, and collection from membrane proteins in lipidic mesophase. Whilst indexing and integration of individual data sets may be relatively straightforward with existing software, merging multiple data sets from small wedges presents new challenges. Identification of a consensus symmetry can be problematic, particularly in the presence of a potential indexing ambiguity. Furthermore, the presence of non-isomorphous or poor-quality data sets may reduce the overall quality of the final merged data set. To facilitate and help optimise the scaling and merging of multiple data sets, we developed a new program, xia2.multiplex, which takes data sets individually integrated with DIALS and performs symmetry analysis, scaling and merging of multi-crystal data sets. xia2.multiplex also performs analysis of various pathologies that typically affect multi-crystal data sets, including non-isomorphism, radiation damage and preferential orientation. After describing a number of use cases, we demonstrate the benefit of xia2.multiplex within a wider autoprocessing framework in facilitating a multi-crystal experiment collected as part of in situ room-temperature fragment screening experiments on the SARS-CoV-2 main protease.

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“…After symmetry determination, an overall best estimate of the unit cell is obtained by refinement of the unit-cell parameters against the observed 2 angles using dials.two_ theta_refine (Winter et al, 2022). This program minimizes the unit-cell constants against the difference between observed and calculated 2 values, which are determined from background-subtracted integrated centroids.…”

Section: Unit-cell Refinementmentioning

confidence: 99%

xia2.multiplex: a multi-crystal data-analysis pipeline

Gildea¹,

Beilsten-Edmands²,

Axford³

et al. 2022

Acta Crystallogr D Struct Biol

Self Cite

View full text Add to dashboard Cite

In macromolecular crystallography, radiation damage limits the amount of data that can be collected from a single crystal. It is often necessary to merge data sets from multiple crystals; for example, small-wedge data collections from micro-crystals, in situ room-temperature data collections and data collection from membrane proteins in lipidic mesophases. Whilst the indexing and integration of individual data sets may be relatively straightforward with existing software, merging multiple data sets from small wedges presents new challenges. The identification of a consensus symmetry can be problematic, particularly in the presence of a potential indexing ambiguity. Furthermore, the presence of non-isomorphous or poor-quality data sets may reduce the overall quality of the final merged data set. To facilitate and help to optimize the scaling and merging of multiple data sets, a new program, xia2.multiplex, has been developed which takes data sets individually integrated with DIALS and performs symmetry analysis, scaling and merging of multi-crystal data sets. xia2.multiplex also performs analysis of various pathologies that typically affect multi-crystal data sets, including non-isomorphism, radiation damage and preferential orientation. After the description of a number of use cases, the benefit of xia2.multiplex is demonstrated within a wider autoprocessing framework in facilitating a multi-crystal experiment collected as part of in situ room-temperature fragment-screening experiments on the SARS-CoV-2 main protease.

show abstract

DIALS as a toolkit

Cited by 78 publications

References 37 publications

Penicillin Derivatives Inhibit the SARS-CoV-2 Main Protease by Reaction with Its Nucleophilic Cysteine

Penicillin Derivatives Inhibit the SARS-CoV-2 Main Protease by Reaction with Its Nucleophilic Cysteine

xia2.multiplex: a multi-crystal data analysis pipeline

xia2.multiplex: a multi-crystal data-analysis pipeline

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