title: Predicting X-ray diffuse scattering from translation-libration-screw structural ensembles.
abstract: Identifying the intramolecular motions of proteins and nucleic acids is a major challenge in macromolecular X-ray crystallography. Because Bragg diffraction describes the average positional distribution of crystalline atoms with imperfect precision, the resulting electron density can be compatible with multiple models of motion. Diffuse X-ray scattering can reduce this degeneracy by reporting on correlated atomic displacements. Although recent technological advances are increasing the potential to accurately measure diffuse scattering, computational modeling and validation tools are still needed to quantify the agreement between experimental data and different parameterizations of crystalline disorder. A new tool, phenix.diffuse, addresses this need by employing Guinier's equation to calculate diffuse scattering from Protein Data Bank (PDB)-formatted structural ensembles. As an example case, phenix.diffuse is applied to translation-libration-screw (TLS) refinement, which models rigid-body displacement for segments of the macromolecule. To enable the calculation of diffuse scattering from TLS-refined structures, phenix.tls_as_xyz builds multi-model PDB files that sample the underlying T, L and S tensors. In the glycerophosphodiesterase GpdQ, alternative TLS-group partitioning and different motional correlations between groups yield markedly dissimilar diffuse scattering maps with distinct implications for molecular mechanism and allostery. These methods demonstrate how, in principle, X-ray diffuse scattering could extend macromolecular structural refinement, validation and analysis.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Van Benschoten
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Pavel V
authors.initials: PV
authors.lastname: Afonine
authors.affiliation: Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Terwilliger
authors.affiliation: Computer, Computational, and Statistical Sciences Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wall
authors.affiliation: Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Jackson
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Sauter
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Adams
authors.affiliation: Centre for Integrative Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-UdS, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Urzhumtsev
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Fraser
mesh_terms: D018360:Crystallography, X-Ray / Q000379:methods*; D030562:Databases, Protein; D008958:Models, Molecular; D009038:Motion; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012542:Scattering, Radiation; D014965:X-Rays
chemical_list: D011506:Proteins
keywords: TLS; correlated motion; diffuse scattering; structural ensemble; structure refinement