IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
SIMBAD: a sequence-independent molecular-replacement pipeline
Autor/es:
WILLIAM SHEPARD; YIBIN XU; MARCIN WOJDYR; ANDREY LEBEDEV; FELIX SIMKOVIC; DANIEL J. RIGDEN; MARÍA-NATALIA LISA; RUI WU; RONAN KEEGAN; VILLE USKI; ALEJANDRO BUSCHIAZZO; JENS M. H. THOMAS; RUSLAN SANISHVILI; CHARLES BALLARD; MARTIN SAVKO; ADAM J. SIMPKIN
Revista:
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Londres; Año: 2018 vol. 74 p. 1 - 11
ISSN:
0907-4449
Resumen:
The conventional approach to finding structurally similar search models for usein molecular replacement (MR) is to use the sequence of the target to searchagainst those of a set of known structures. Sequence similarity often correlateswith structure similarity. Given sufficient similarity, a known structure correctlypositioned in the target cell by the MR process can provide an approximationto the unknown phases of the target. An alternative approach to identifyinghomologous structures suitable for MR is to exploit the measured data directly,comparing the lattice parameters or the experimentally derived structure-factoramplitudes with those of known structures. Here, SIMBAD, a new sequenceindependentMR pipeline which implements these approaches, is presented.SIMBAD can identify cases of contaminant crystallization and other mishapssuch as mistaken identity (swapped crystallization trays), as well as solvingunsequenced targets and providing a brute-force approach where sequencedependentsearch-model identification may be nontrivial, for example becauseof conformational diversity among identifiable homologues. The programimplements a three-step pipeline to efficiently identify a suitable search model ina database of known structures. The first step performs a lattice-parametersearch against the entire Protein Data Bank (PDB), rapidly determiningwhether or not a homologue exists in the same crystal form. The second step isdesigned to screen the target data for the presence of a crystallized contaminant,a not uncommon occurrence in macromolecular crystallography. Solvingstructures with MR in such cases can remain problematic for many years, sincethe search models, which are assumed to be similar to the structure of interest,are not necessarily related to the structures that have actually crystallized. Tocater for this eventuality, SIMBAD rapidly screens the data against a databaseof known contaminant structures. Where the first two steps fail to yield asolution, a final step in SIMBAD can be invoked to perform a brute-force searchof a nonredundant PDB database provided by the MoRDa MR software.Through early-access usage of SIMBAD, this approach has solved novel casesthat have otherwise proved difficult to solve.