Finke, A. D. | bioRxiv Science

bioRxiv2026

Simulating Neutron Protein Crystallography Experiments: Applications to the Development of the NMX Instrument at ESS

Monte Carlo neutron ray-tracing simulations of time-of-flight (TOF)-Laue neutron macromolecular crystal diffraction (n-MX) using the McStas software package were done for the upcoming NMX Macromolecular Diffractometer at the European Spallation Source. Splitting neutron rays that arrive at the crystal lead to dramatic improvements in event formation with minimal computational overhead. The simulated event probability data was sampled using a new single-pass weighted reservoir sampling method, and processed like real n-MX data using DIALS. The effects of air and beamstop scatter on simulated data was investigated. SynopsisMonte Carlo simulations of neutron protein diffraction experiments provide useful data that models instrumental components that interact with neutrons, as well as the crystal diffraction itself. These data can be applied to instrument development, such as the commissioning of the NMX Macromolecular Diffractometer at ESS.

biophysics↗

bioRxiv2023

Pushed to extremes: distinct effects of high temperature vs. pressure on the structure of an atypical phosphatase

Protein function hinges on small shifts of three-dimensional structure. Elevating temperature or pressure may provide experimentally accessible insights into such shifts, but the effects of these distinct perturbations on protein structures have not been compared in atomic detail. To quantitatively explore these two axes, we report the first pair of structures at physiological temperature vs. high pressure for the same protein, STEP (PTPN5). We show that these perturbations have distinct and surprising effects on protein volume, patterns of ordered solvent, and local backbone and side-chain conformations. This includes novel interactions between key catalytic loops only at physiological temperature, and a distinct conformational ensemble for another active-site loop only at high pressure. Strikingly, in torsional space, physiological temperature shifts STEP toward previously reported active-like states, while high pressure shifts it toward a previously uncharted region. Together, our work argues that temperature and pressure are complementary, powerful, fundamental macromolecular perturbations.

biophysics↗