Phase Combination and its Application to the Solution of Macromolecular Structures: Developing ALIXE and SHREDDER

[eng] Phasing X-ray data within the frame of the ARCIMBOLDO programs requires very accurate models and a sophisticated evaluation of the possible hypotheses. ARCIMBOLDO uses small fragments, that are placed with the maximum likelihood molecular replacement program Phaser, and are subject to density...

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Author: Millán Nebot, Claudia Lucía
Format: doctoral thesis
Status:Published version
Publication Date:2018
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/125131
Online Access:https://hdl.handle.net/2445/125131
http://hdl.handle.net/10803/663022
Access Level:Open access
Keyword:Biologia molecular
Proteòmica
Macromolècules
Cristal·lografia
Estructura cristal·lina (Sòlids)
Molecular biology
Proteomics
Macromolecules
Crystallography
Layer structure (Solids)
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spelling Phase Combination and its Application to the Solution of Macromolecular Structures: Developing ALIXE and SHREDDERMillán Nebot, Claudia LucíaBiologia molecularProteòmicaMacromolèculesCristal·lografiaEstructura cristal·lina (Sòlids)Molecular biologyProteomicsMacromoleculesCrystallographyLayer structure (Solids)[eng] Phasing X-ray data within the frame of the ARCIMBOLDO programs requires very accurate models and a sophisticated evaluation of the possible hypotheses. ARCIMBOLDO uses small fragments, that are placed with the maximum likelihood molecular replacement program Phaser, and are subject to density modification and autotracing with the program SHELXE. The software receives its name from the Italian painter Giuseppe Arcimboldo, who used to compose portraits out of common objects such as vegetables or flowers. Out of most possible arrangements of such objects, only a still-life will result, and just a few ones will truly produce a portrait. In a similar way, from all possible placements with small protein fragments, only a few will be correct and will allow to get the full “protein’s portrait”. The work presented in this thesis has explored new ways to exploit partial information and increase the signal in the process of phasing with fragments. This has been achieved through two main pieces of software, ALIXE and SHREDDER. With the spherical mode in ARCIMBOLDO_SHREDDER, the aim is to derive compact fragments starting from a distant homolog to our unknown protein of interest. Then, locations for these fragments are searched with Phaser. These include strategies for refining the fragments against the experimental data and giving them more degrees of freedom. With ALIXE, the aim is to combine information in reciprocal space from partial solutions, such as the ones produced by SHREDDER, and use the coherence between them to guide their merging and to increase the information content, so that the step of density modification and autotracing starts from a more complete solution. Even if partial solutions contain both correct and incorrect information, the combination of solutions that share some similarity will allow to get a better approximation to the correct structure. Both ARCIMBOLDO_SHREDDER and ALIXE have been used on test data for development and optimisation but also on datasets from previously unknown structures, which have been solved thanks to these programs. These programs are distributed through the website of the group but also through software suites of general use in the crystallographic community such as CCP4 and SBGrid.Universitat de BarcelonaUsón Finkenzeller, IsabelUniversitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació2018info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/125131http://hdl.handle.net/10803/663022Tesis Doctorals - Facultat - Farmàcia i Ciències de l'Alimentacióreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaIngléscc-by-nc-sa, (c) Millán, 2018http://creativecommons.org/licenses/by-nc-sa/3.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1251312026-05-27T06:46:51Z
dc.title.none.fl_str_mv Phase Combination and its Application to the Solution of Macromolecular Structures: Developing ALIXE and SHREDDER
title Phase Combination and its Application to the Solution of Macromolecular Structures: Developing ALIXE and SHREDDER
spellingShingle Phase Combination and its Application to the Solution of Macromolecular Structures: Developing ALIXE and SHREDDER
Millán Nebot, Claudia Lucía
Biologia molecular
Proteòmica
Macromolècules
Cristal·lografia
Estructura cristal·lina (Sòlids)
Molecular biology
Proteomics
Macromolecules
Crystallography
Layer structure (Solids)
title_short Phase Combination and its Application to the Solution of Macromolecular Structures: Developing ALIXE and SHREDDER
title_full Phase Combination and its Application to the Solution of Macromolecular Structures: Developing ALIXE and SHREDDER
title_fullStr Phase Combination and its Application to the Solution of Macromolecular Structures: Developing ALIXE and SHREDDER
title_full_unstemmed Phase Combination and its Application to the Solution of Macromolecular Structures: Developing ALIXE and SHREDDER
title_sort Phase Combination and its Application to the Solution of Macromolecular Structures: Developing ALIXE and SHREDDER
dc.creator.none.fl_str_mv Millán Nebot, Claudia Lucía
author Millán Nebot, Claudia Lucía
author_facet Millán Nebot, Claudia Lucía
author_role author
dc.contributor.none.fl_str_mv Usón Finkenzeller, Isabel
Universitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació
dc.subject.none.fl_str_mv Biologia molecular
Proteòmica
Macromolècules
Cristal·lografia
Estructura cristal·lina (Sòlids)
Molecular biology
Proteomics
Macromolecules
Crystallography
Layer structure (Solids)
topic Biologia molecular
Proteòmica
Macromolècules
Cristal·lografia
Estructura cristal·lina (Sòlids)
Molecular biology
Proteomics
Macromolecules
Crystallography
Layer structure (Solids)
description [eng] Phasing X-ray data within the frame of the ARCIMBOLDO programs requires very accurate models and a sophisticated evaluation of the possible hypotheses. ARCIMBOLDO uses small fragments, that are placed with the maximum likelihood molecular replacement program Phaser, and are subject to density modification and autotracing with the program SHELXE. The software receives its name from the Italian painter Giuseppe Arcimboldo, who used to compose portraits out of common objects such as vegetables or flowers. Out of most possible arrangements of such objects, only a still-life will result, and just a few ones will truly produce a portrait. In a similar way, from all possible placements with small protein fragments, only a few will be correct and will allow to get the full “protein’s portrait”. The work presented in this thesis has explored new ways to exploit partial information and increase the signal in the process of phasing with fragments. This has been achieved through two main pieces of software, ALIXE and SHREDDER. With the spherical mode in ARCIMBOLDO_SHREDDER, the aim is to derive compact fragments starting from a distant homolog to our unknown protein of interest. Then, locations for these fragments are searched with Phaser. These include strategies for refining the fragments against the experimental data and giving them more degrees of freedom. With ALIXE, the aim is to combine information in reciprocal space from partial solutions, such as the ones produced by SHREDDER, and use the coherence between them to guide their merging and to increase the information content, so that the step of density modification and autotracing starts from a more complete solution. Even if partial solutions contain both correct and incorrect information, the combination of solutions that share some similarity will allow to get a better approximation to the correct structure. Both ARCIMBOLDO_SHREDDER and ALIXE have been used on test data for development and optimisation but also on datasets from previously unknown structures, which have been solved thanks to these programs. These programs are distributed through the website of the group but also through software suites of general use in the crystallographic community such as CCP4 and SBGrid.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/125131
http://hdl.handle.net/10803/663022
url https://hdl.handle.net/2445/125131
http://hdl.handle.net/10803/663022
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv cc-by-nc-sa, (c) Millán, 2018
http://creativecommons.org/licenses/by-nc-sa/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-sa, (c) Millán, 2018
http://creativecommons.org/licenses/by-nc-sa/3.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Facultat - Farmàcia i Ciències de l'Alimentació
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869408166862651392
score 15,300719

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