@article{2fff9f300c7c4271979e0708cb7eaa24,
title = "Reproducibility of protein x-ray diffuse scattering and potential utility for modeling atomic displacement parameters",
abstract = "Protein structure and dynamics can be probed using x-ray crystallography. Whereas the Bragg peaks are only sensitive to the average unit-cell electron density, the signal between the Bragg peaks—diffuse scattering—is sensitive to spatial correlations in electron-density variations. Although diffuse scattering contains valuable information about protein dynamics, the diffuse signal is more difficult to isolate from the background compared to the Bragg signal, and the reproducibility of diffuse signal is not yet well understood. We present a systematic study of the reproducibility of diffuse scattering from isocyanide hydratase in three different protein forms. Both replicate diffuse datasets and datasets obtained from different mutants were similar in pairwise comparisons (Pearson correlation coefficient ≥0.8). The data were processed in a manner inspired by previously published methods using custom software with modular design, enabling us to perform an analysis of various data processing choices to determine how to obtain the highest quality data as assessed using unbiased measures of symmetry and reproducibility. The diffuse data were then used to characterize atomic mobility using a liquid-like motions (LLM) model. This characterization was able to discriminate between distinct anisotropic atomic displacement parameter (ADP) models arising from different anisotropic scaling choices that agreed comparably with the Bragg data. Our results emphasize the importance of data reproducibility as a model-free measure of diffuse data quality, illustrate the ability of LLM analysis of diffuse scattering to select among alternative ADP models, and offer insights into the design of successful diffuse scattering experiments.",
author = "Zhen Su and Medhanjali Dasgupta and Fr{\'e}d{\'e}ric Poitevin and Mathews, {Irimpan I.} and {van den Bedem}, Henry and Wall, {Michael E.} and Yoon, {Chun Hong} and Wilson, {Mark A.}",
note = "Funding Information: The authors are grateful to Steve P. Meisburger for comments that led to substantial improvements in the manuscript and insights that enabled us to determine the source of the difference in ADPs between the PHENIX and Refmac5 models. Z.S. would like to thank Professor Mike Dunne for his guidance and support, and Professor James Holton for the discussion on x-ray cross sections of glasses and plastics. C.H.Y acknowledges support from the Exascale Computing Project (No. 17-SC-20-SC). M.A.W. acknowledges support from NIH R01GM139978. H.v.d.B. was supported by NIH R01GM123159 and by a Mercator Fellowship from the Deutsche Forschungsgemeinschaft (No. LE 1841/5-1). M.E.W. was supported by the Exascale Computing Project (No. 17-SC-20-SC), a collaborative effort of the U.S. Department of Energy Office of Science and the National Nuclear Security Administration, and the University of California Laboratory Fees Research Program (No. LFR-17-476732). Use of the Stanford Synchrotron Radiation Lightsource and Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (No. P30GM133894). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NIGMS or NIH. The Los Alamos National Laboratory technical release number of this article is LAUR-22724. Publisher Copyright: {\textcopyright} 2021 Author(s).",
year = "2021",
month = jul,
day = "1",
doi = "10.1063/4.0000087",
language = "English (US)",
volume = "8",
journal = "Structural Dynamics",
issn = "2329-7778",
publisher = "AAPM - American Association of Physicists in Medicine",
number = "4",
}