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Title: Improved crystallographic models through iterated local density-guided model deformation and reciprocal-space refinement

Abstract

A density-based procedure is described for improving a homology model that is locally accurate but differs globally. The model is deformed to match the map and refined, yielding an improved starting point for density modification and further model-building. An approach is presented for addressing the challenge of model rebuilding after molecular replacement in cases where the placed template is very different from the structure to be determined. The approach takes advantage of the observation that a template and target structure may have local structures that can be superimposed much more closely than can their complete structures. A density-guided procedure for deformation of a properly placed template is introduced. A shift in the coordinates of each residue in the structure is calculated based on optimizing the match of model density within a 6 Å radius of the center of that residue with a prime-and-switch electron-density map. The shifts are smoothed and applied to the atoms in each residue, leading to local deformation of the template that improves the match of map and model. The model is then refined to improve the geometry and the fit of model to the structure-factor data. A new map is then calculated and the process ismore » repeated until convergence. The procedure can extend the routine applicability of automated molecular replacement, model building and refinement to search models with over 2 Å r.m.s.d. representing 65–100% of the structure.« less

Authors:
 [1];  [2];  [3];  [4]; ;  [3];  [1]
  1. Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)
  2. University of Cambridge, Cambridge CB2 0XY (United Kingdom)
  3. Lawrence Berkeley National Laboratory, One Cyclotron Road, Building 64R0121, Berkeley, CA 94720 (United States)
  4. Stanford University, 318 Campus Drive West, Stanford, CA 94305-5432 (United States)
Publication Date:
OSTI Identifier:
22347886
Resource Type:
Journal Article
Journal Name:
Acta Crystallographica. Section D: Biological Crystallography
Additional Journal Information:
Journal Volume: 68; Journal Issue: Pt 7; Other Information: PMCID: PMC3388814; PMID: 22751672; PUBLISHER-ID: kw5044; OAI: oai:pubmedcentral.nih.gov:3388814; Copyright (c) Terwilliger et al. 2012; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0907-4449
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; ATOMS; CONVERGENCE; CRYSTALS; DEFORMATION; DENSITY; ELECTRON DENSITY; ELECTRONS; GEOMETRY; MODIFICATIONS; SIMULATION; STRUCTURE FACTORS; SWITCHES

Citation Formats

Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov, Read, Randy J., Adams, Paul D., Brunger, Axel T., Afonine, Pavel V., Grosse-Kunstleve, Ralf W., and Hung, Li-Wei. Improved crystallographic models through iterated local density-guided model deformation and reciprocal-space refinement. Denmark: N. p., 2012. Web. doi:10.1107/S0907444912015636.
Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov, Read, Randy J., Adams, Paul D., Brunger, Axel T., Afonine, Pavel V., Grosse-Kunstleve, Ralf W., & Hung, Li-Wei. Improved crystallographic models through iterated local density-guided model deformation and reciprocal-space refinement. Denmark. doi:10.1107/S0907444912015636.
Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov, Read, Randy J., Adams, Paul D., Brunger, Axel T., Afonine, Pavel V., Grosse-Kunstleve, Ralf W., and Hung, Li-Wei. Sun . "Improved crystallographic models through iterated local density-guided model deformation and reciprocal-space refinement". Denmark. doi:10.1107/S0907444912015636.
@article{osti_22347886,
title = {Improved crystallographic models through iterated local density-guided model deformation and reciprocal-space refinement},
author = {Terwilliger, Thomas C., E-mail: terwilliger@lanl.gov and Read, Randy J. and Adams, Paul D. and Brunger, Axel T. and Afonine, Pavel V. and Grosse-Kunstleve, Ralf W. and Hung, Li-Wei},
abstractNote = {A density-based procedure is described for improving a homology model that is locally accurate but differs globally. The model is deformed to match the map and refined, yielding an improved starting point for density modification and further model-building. An approach is presented for addressing the challenge of model rebuilding after molecular replacement in cases where the placed template is very different from the structure to be determined. The approach takes advantage of the observation that a template and target structure may have local structures that can be superimposed much more closely than can their complete structures. A density-guided procedure for deformation of a properly placed template is introduced. A shift in the coordinates of each residue in the structure is calculated based on optimizing the match of model density within a 6 Å radius of the center of that residue with a prime-and-switch electron-density map. The shifts are smoothed and applied to the atoms in each residue, leading to local deformation of the template that improves the match of map and model. The model is then refined to improve the geometry and the fit of model to the structure-factor data. A new map is then calculated and the process is repeated until convergence. The procedure can extend the routine applicability of automated molecular replacement, model building and refinement to search models with over 2 Å r.m.s.d. representing 65–100% of the structure.},
doi = {10.1107/S0907444912015636},
journal = {Acta Crystallographica. Section D: Biological Crystallography},
issn = {0907-4449},
number = Pt 7,
volume = 68,
place = {Denmark},
year = {2012},
month = {7}
}