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Title: Prospects for de novo phasing with de novo protein models

Abstract

In a first systematic exploration of phasing with Rosetta de novo models, it is shown that all-atom refinement of coarse-grained models significantly improves both the model quality and performance in molecular replacement with the Phaser software. The prospect of phasing diffraction data sets ‘de novo’ for proteins with previously unseen folds is appealing but largely untested. In a first systematic exploration of phasing with Rosetta de novo models, it is shown that all-atom refinement of coarse-grained models significantly improves both the model quality and performance in molecular replacement with the Phaser software. 15 new cases of diffraction data sets that are unambiguously phased with de novo models are presented. These diffraction data sets represent nine space groups and span a large range of solvent contents (33–79%) and asymmetric unit copy numbers (1–4). No correlation is observed between the ease of phasing and the solvent content or asymmetric unit copy number. Instead, a weak correlation is found with the length of the modeled protein: larger proteins required somewhat less accurate models to give successful molecular replacement. Overall, the results of this survey suggest that de novo models can phase diffraction data for approximately one sixth of proteins with sizes of 100more » residues or less. However, for many of these cases, ‘de novo phasing with de novo models’ requires significant investment of computational power, much greater than 10{sup 3} CPU days per target. Improvements in conformational search methods will be necessary if molecular replacement with de novo models is to become a practical tool for targets without homology to previously solved protein structures.« less

Authors:
;  [1]
  1. Department of Biochemistry, University of Washington, Seattle, WA 98195 (United States)
Publication Date:
OSTI Identifier:
22347973
Resource Type:
Journal Article
Journal Name:
Acta Crystallographica. Section D: Biological Crystallography
Additional Journal Information:
Journal Volume: 65; Journal Issue: Pt 2; Other Information: PMCID: PMC2631639; PMID: 19171972; PUBLISHER-ID: ba5122; OAI: oai:pubmedcentral.nih.gov:2631639; Copyright (c) Das & Baker 2009; 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; CORRELATIONS; DIFFRACTION; LENGTH; PERFORMANCE; PROTEIN STRUCTURE; PROTEINS; SOLVENTS; SPACE GROUPS

Citation Formats

Das, Rhiju, and Baker, David. Prospects for de novo phasing with de novo protein models. Denmark: N. p., 2009. Web. doi:10.1107/S0907444908020039.
Das, Rhiju, & Baker, David. Prospects for de novo phasing with de novo protein models. Denmark. https://doi.org/10.1107/S0907444908020039
Das, Rhiju, and Baker, David. 2009. "Prospects for de novo phasing with de novo protein models". Denmark. https://doi.org/10.1107/S0907444908020039.
@article{osti_22347973,
title = {Prospects for de novo phasing with de novo protein models},
author = {Das, Rhiju and Baker, David},
abstractNote = {In a first systematic exploration of phasing with Rosetta de novo models, it is shown that all-atom refinement of coarse-grained models significantly improves both the model quality and performance in molecular replacement with the Phaser software. The prospect of phasing diffraction data sets ‘de novo’ for proteins with previously unseen folds is appealing but largely untested. In a first systematic exploration of phasing with Rosetta de novo models, it is shown that all-atom refinement of coarse-grained models significantly improves both the model quality and performance in molecular replacement with the Phaser software. 15 new cases of diffraction data sets that are unambiguously phased with de novo models are presented. These diffraction data sets represent nine space groups and span a large range of solvent contents (33–79%) and asymmetric unit copy numbers (1–4). No correlation is observed between the ease of phasing and the solvent content or asymmetric unit copy number. Instead, a weak correlation is found with the length of the modeled protein: larger proteins required somewhat less accurate models to give successful molecular replacement. Overall, the results of this survey suggest that de novo models can phase diffraction data for approximately one sixth of proteins with sizes of 100 residues or less. However, for many of these cases, ‘de novo phasing with de novo models’ requires significant investment of computational power, much greater than 10{sup 3} CPU days per target. Improvements in conformational search methods will be necessary if molecular replacement with de novo models is to become a practical tool for targets without homology to previously solved protein structures.},
doi = {10.1107/S0907444908020039},
url = {https://www.osti.gov/biblio/22347973}, journal = {Acta Crystallographica. Section D: Biological Crystallography},
issn = {0907-4449},
number = Pt 2,
volume = 65,
place = {Denmark},
year = {Sun Feb 01 00:00:00 EST 2009},
month = {Sun Feb 01 00:00:00 EST 2009}
}