Understanding the molecular bases behind congenital disorders of glycosylation
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Tipo de documento: | Dissertação |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.22/24780 |
Resumo: | Congenital disorders of glycosylation (CDG) result from mutations affecting proteins involved in glycosylation pathways. Phosphomannomutase 2 (PMM2) deficiency (PMM2-CDG), the most common N-glycosylation disorder, induces hypoglycosylation of several proteins leading to multisystem involvement. This disease is related to a huge variety of mutante variants and a broad phenotypic spectrum, making genitype-phenotype correlations difficult. Mutations in PMM2 can affect is structure and function and may reveal a specific phenotype, One possible strategy for studying genotype-phenotype correlations would be to apply computational methods to assess the structural changes caused by amino acid substitutions. This would allow further development of personalised therapies for na untreatable disease. With the aim of developing na in silico protocol to analyse the impacto f diferente mutations on PMM2., several three-dimensional structures of mutated PMM2 were modelled and molecular Dynamics (MD) simulations were analysed to assess the impact of these variants at he energetic and molecular level on the normal activity of PMM2, including dimerization, folding, substrate-binding and structure-stability. The results predict the effect of missense mutations on the function of PMM2, in particular on the free energy of dimerization and folding of the protein. |
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Understanding the molecular bases behind congenital disorders of glycosylationComputacional methodsMolecular dynamicsGenotype-phenotype correlationPMM2PMM2-CDGCongenital disorders of glycosylation (CDG) result from mutations affecting proteins involved in glycosylation pathways. Phosphomannomutase 2 (PMM2) deficiency (PMM2-CDG), the most common N-glycosylation disorder, induces hypoglycosylation of several proteins leading to multisystem involvement. This disease is related to a huge variety of mutante variants and a broad phenotypic spectrum, making genitype-phenotype correlations difficult. Mutations in PMM2 can affect is structure and function and may reveal a specific phenotype, One possible strategy for studying genotype-phenotype correlations would be to apply computational methods to assess the structural changes caused by amino acid substitutions. This would allow further development of personalised therapies for na untreatable disease. With the aim of developing na in silico protocol to analyse the impacto f diferente mutations on PMM2., several three-dimensional structures of mutated PMM2 were modelled and molecular Dynamics (MD) simulations were analysed to assess the impact of these variants at he energetic and molecular level on the normal activity of PMM2, including dimerization, folding, substrate-binding and structure-stability. The results predict the effect of missense mutations on the function of PMM2, in particular on the free energy of dimerization and folding of the protein.Sousa, SérgioFerraz, RicardoRepositório Científico do Instituto Politécnico do PortoOliveira, Tiago André Cunha2023-11-222026-11-22T00:00:00Z2023-11-22T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.22/24780TID:203472993enginfo:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-14T01:46:10Zoai:recipp.ipp.pt:10400.22/24780Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T01:59:08.829227Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Understanding the molecular bases behind congenital disorders of glycosylation |
title |
Understanding the molecular bases behind congenital disorders of glycosylation |
spellingShingle |
Understanding the molecular bases behind congenital disorders of glycosylation Oliveira, Tiago André Cunha Computacional methods Molecular dynamics Genotype-phenotype correlation PMM2 PMM2-CDG |
title_short |
Understanding the molecular bases behind congenital disorders of glycosylation |
title_full |
Understanding the molecular bases behind congenital disorders of glycosylation |
title_fullStr |
Understanding the molecular bases behind congenital disorders of glycosylation |
title_full_unstemmed |
Understanding the molecular bases behind congenital disorders of glycosylation |
title_sort |
Understanding the molecular bases behind congenital disorders of glycosylation |
author |
Oliveira, Tiago André Cunha |
author_facet |
Oliveira, Tiago André Cunha |
author_role |
author |
dc.contributor.none.fl_str_mv |
Sousa, Sérgio Ferraz, Ricardo Repositório Científico do Instituto Politécnico do Porto |
dc.contributor.author.fl_str_mv |
Oliveira, Tiago André Cunha |
dc.subject.por.fl_str_mv |
Computacional methods Molecular dynamics Genotype-phenotype correlation PMM2 PMM2-CDG |
topic |
Computacional methods Molecular dynamics Genotype-phenotype correlation PMM2 PMM2-CDG |
description |
Congenital disorders of glycosylation (CDG) result from mutations affecting proteins involved in glycosylation pathways. Phosphomannomutase 2 (PMM2) deficiency (PMM2-CDG), the most common N-glycosylation disorder, induces hypoglycosylation of several proteins leading to multisystem involvement. This disease is related to a huge variety of mutante variants and a broad phenotypic spectrum, making genitype-phenotype correlations difficult. Mutations in PMM2 can affect is structure and function and may reveal a specific phenotype, One possible strategy for studying genotype-phenotype correlations would be to apply computational methods to assess the structural changes caused by amino acid substitutions. This would allow further development of personalised therapies for na untreatable disease. With the aim of developing na in silico protocol to analyse the impacto f diferente mutations on PMM2., several three-dimensional structures of mutated PMM2 were modelled and molecular Dynamics (MD) simulations were analysed to assess the impact of these variants at he energetic and molecular level on the normal activity of PMM2, including dimerization, folding, substrate-binding and structure-stability. The results predict the effect of missense mutations on the function of PMM2, in particular on the free energy of dimerization and folding of the protein. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-11-22 2023-11-22T00:00:00Z 2026-11-22T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.22/24780 TID:203472993 |
url |
http://hdl.handle.net/10400.22/24780 |
identifier_str_mv |
TID:203472993 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
eu_rights_str_mv |
embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799137075427016704 |