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Title: Interpretation of ensembles created by multiple iterative rebuilding of macromolecular models

Abstract

Heterogeneity in ensembles generated by independent model rebuilding principally reflects the limitations of the data and of the model-building process rather than the diversity of structures in the crystal. Automation of iterative model building, density modification and refinement in macromolecular crystallography has made it feasible to carry out this entire process multiple times. By using different random seeds in the process, a number of different models compatible with experimental data can be created. Sets of models were generated in this way using real data for ten protein structures from the Protein Data Bank and using synthetic data generated at various resolutions. Most of the heterogeneity among models produced in this way is in the side chains and loops on the protein surface. Possible interpretations of the variation among models created by repetitive rebuilding were investigated. Synthetic data were created in which a crystal structure was modelled as the average of a set of ‘perfect’ structures and the range of models obtained by rebuilding a single starting model was examined. The standard deviations of coordinates in models obtained by repetitive rebuilding at high resolution are small, while those obtained for the same synthetic crystal structure at low resolution are large, somore » that the diversity within a group of models cannot generally be a quantitative reflection of the actual structures in a crystal. Instead, the group of structures obtained by repetitive rebuilding reflects the precision of the models, and the standard deviation of coordinates of these structures is a lower bound estimate of the uncertainty in coordinates of the individual models.« less

Authors:
 [1]; ; ; ; ;  [2];  [3];  [4];  [1]
  1. Los Alamos National Laboratory, Mailstop M888, Los Alamos, NM 87545 (United States)
  2. Lawrence Berkeley National Laboratory, One Cyclotron Road, Building 64R0121, Berkeley, CA 94720 (United States)
  3. Department of Haematology, University of Cambridge, Cambridge CB2 0XY (United Kingdom)
  4. Jozef Stefan Institute, Jamova 39, 1000 Ljubljana (Slovenia)
Publication Date:
OSTI Identifier:
22348005
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section D: Biological Crystallography; Journal Volume: 63; Journal Issue: Pt 5; Other Information: PMCID: PMC2483474; PUBLISHER-ID: wd5073; PMID: 17452785; OAI: oai:pubmedcentral.nih.gov:2483474; Copyright (c) International Union of Crystallography 2007; This is an open-access article distributed under the terms described at http://journals.iucr.org/services/termsofuse.html.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; ACCURACY; CHAINS; CONVERGENCE; CRYSTAL STRUCTURE; CRYSTALS; DENSITY; EXPERIMENTAL DATA; MODIFICATIONS; PROTEIN STRUCTURE; PROTEINS; REFLECTION; RESOLUTION; SURFACES; VARIATIONS

Citation Formats

Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov, Grosse-Kunstleve, Ralf W., Afonine, Pavel V., Adams, Paul D., Moriarty, Nigel W., Zwart, Peter, Read, Randy J., Turk, Dusan, and Hung, Li-Wei. Interpretation of ensembles created by multiple iterative rebuilding of macromolecular models. Denmark: N. p., 2007. Web. doi:10.1107/S0907444907009791.
Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov, Grosse-Kunstleve, Ralf W., Afonine, Pavel V., Adams, Paul D., Moriarty, Nigel W., Zwart, Peter, Read, Randy J., Turk, Dusan, & Hung, Li-Wei. Interpretation of ensembles created by multiple iterative rebuilding of macromolecular models. Denmark. doi:10.1107/S0907444907009791.
Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov, Grosse-Kunstleve, Ralf W., Afonine, Pavel V., Adams, Paul D., Moriarty, Nigel W., Zwart, Peter, Read, Randy J., Turk, Dusan, and Hung, Li-Wei. Tue . "Interpretation of ensembles created by multiple iterative rebuilding of macromolecular models". Denmark. doi:10.1107/S0907444907009791.
@article{osti_22348005,
title = {Interpretation of ensembles created by multiple iterative rebuilding of macromolecular models},
author = {Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov and Grosse-Kunstleve, Ralf W. and Afonine, Pavel V. and Adams, Paul D. and Moriarty, Nigel W. and Zwart, Peter and Read, Randy J. and Turk, Dusan and Hung, Li-Wei},
abstractNote = {Heterogeneity in ensembles generated by independent model rebuilding principally reflects the limitations of the data and of the model-building process rather than the diversity of structures in the crystal. Automation of iterative model building, density modification and refinement in macromolecular crystallography has made it feasible to carry out this entire process multiple times. By using different random seeds in the process, a number of different models compatible with experimental data can be created. Sets of models were generated in this way using real data for ten protein structures from the Protein Data Bank and using synthetic data generated at various resolutions. Most of the heterogeneity among models produced in this way is in the side chains and loops on the protein surface. Possible interpretations of the variation among models created by repetitive rebuilding were investigated. Synthetic data were created in which a crystal structure was modelled as the average of a set of ‘perfect’ structures and the range of models obtained by rebuilding a single starting model was examined. The standard deviations of coordinates in models obtained by repetitive rebuilding at high resolution are small, while those obtained for the same synthetic crystal structure at low resolution are large, so that the diversity within a group of models cannot generally be a quantitative reflection of the actual structures in a crystal. Instead, the group of structures obtained by repetitive rebuilding reflects the precision of the models, and the standard deviation of coordinates of these structures is a lower bound estimate of the uncertainty in coordinates of the individual models.},
doi = {10.1107/S0907444907009791},
journal = {Acta Crystallographica. Section D: Biological Crystallography},
number = Pt 5,
volume = 63,
place = {Denmark},
year = {Tue May 01 00:00:00 EDT 2007},
month = {Tue May 01 00:00:00 EDT 2007}
}