Scaling and merging time-resolved pink-beam diffraction with variational inference.

Time-resolved x-ray crystallography (TR-X) at synchrotrons and free electron lasers is a promising technique for recording dynamics of molecules at atomic resolution. While experimental methods for TR-X have proliferated and matured, data analysis is often difficult. Extracting small, time-dependent changes in signal is frequently a bottleneck for practitioners.

Laue-DIALS: Open-source software for polychromatic x-ray diffraction data.

Most x-ray sources are inherently polychromatic. Polychromatic ("pink") x-rays provide an efficient way to conduct diffraction experiments as many more photons can be used and large regions of reciprocal space can be probed without sample rotation during exposure-ideal conditions for time-resolved applications. Analysis of such data is complicated, however, causing most x-ray facilities to discard >99% of x-ray photons to obtain monochromatic data.

Scaling and Merging Time-Resolved Laue Data with Variational Inference.

Time-resolved X-ray crystallography (TR-X) at synchrotrons and free electron lasers is a promising technique for recording dynamics of molecules at atomic resolution. While experimental methods for TR-X have proliferated and matured, data analysis is often difficult. Extracting small, time-dependent changes in signal is frequently a bottleneck for practitioners.

Sensitive Detection of Structural Differences using a Statistical Framework for Comparative Crystallography.

Chemical and conformational changes underlie the functional cycles of proteins. Comparative crystallography can reveal these changes over time, over ligands, and over chemical and physical perturbations in atomic detail. A key difficulty, however, is that the resulting observations must be placed on the same scale by correcting for experimental factors.

Laue-DIALS: open-source software for polychromatic X-ray diffraction data.

Most X-ray sources are inherently polychromatic. Polychromatic ("pink") X-rays provide an efficient way to conduct diffraction experiments as many more photons can be used and large regions of reciprocal space can be probed without sample rotation during exposure-ideal conditions for time-resolved applications. Analysis of such data is complicated, however, causing most X-ray facilities to discard >99% of X-ray photons to obtain monochromatic data.

Perturbative diffraction methods resolve a conformational switch that facilitates a two-step enzymatic mechanism.

Enzymes catalyze biochemical reactions through precise positioning of substrates, cofactors, and amino acids to modulate the transition-state free energy. However, the role of conformational dynamics remains poorly understood due to poor experimental access. This shortcoming is evident with dihydrofolate reductase (DHFR), a model system for the role of protein dynamics in catalysis, for which it is unknown how the enzyme regulates the different active site environments required to facilitate proton and hydride transfer.

Correcting systematic errors in diffraction data with modern scaling algorithms.

X-ray diffraction enables the routine determination of the atomic structure of materials. Key to its success are data-processing algorithms that allow experimenters to determine the electron density of a sample from its diffraction pattern. Scaling, the estimation and correction of systematic errors in diffraction intensities, is an essential step in this process.

Resolving conformational changes that mediate a two-step catalytic mechanism in a model enzyme.

Enzymes catalyze biochemical reactions through precise positioning of substrates, cofactors, and amino acids to modulate the transition-state free energy. However, the role of conformational dynamics remains poorly understood due to lack of experimental access. This shortcoming is evident with dihydrofolate reductase (DHFR), a model system for the role of protein dynamics in catalysis, for which it is unknown how the enzyme regulates the different active site environments required to facilitate proton and hydride transfer.

A unifying Bayesian framework for merging X-ray diffraction data.

Novel X-ray methods are transforming the study of the functional dynamics of biomolecules. Key to this revolution is detection of often subtle conformational changes from diffraction data. Diffraction data contain patterns of bright spots known as reflections.

: a Python library for crystallographic data analysis.

Crystallography uses the diffraction of X-rays, electrons or neutrons by crystals to provide invaluable data on the atomic structure of matter, from single atoms to ribosomes. Much of crystallography's success is due to the software packages developed to enable automated processing of diffraction data. However, the analysis of unconventional diffraction experiments can still pose significant challenges - many existing programs are closed source, sparsely documented, or challenging to integrate with modern libraries for scientific computing and machine learning.

The dynamic conformational cycle of the group I chaperonin C-termini revealed via molecular dynamics simulation.

Chaperonins are large ring shaped oligomers that facilitate protein folding by encapsulation within a central cavity. All chaperonins possess flexible C-termini which protrude from the equatorial domain of each subunit into the central cavity. Biochemical evidence suggests that the termini play an important role in the allosteric regulation of the ATPase cycle, in substrate folding and in complex assembly and stability.

A conserved mode of protein recognition and binding in a ParD-ParE toxin-antitoxin complex.

Toxin-antitoxin (TA) systems form a ubiquitous class of prokaryotic proteins with functional roles in plasmid inheritance, environmental stress response, and cell development. ParDE family TA systems are broadly conserved on plasmids and bacterial chromosomes and have been well characterized as genetic elements that promote stable plasmid inheritance. We present a crystal structure of a chromosomally encoded ParD-ParE complex from Caulobacter crescentus at 2.