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Understanding the molecular bases behind congenital disorders of glycosylation

2023-11-22Master thesis Embargoed access
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dc.contributor.advisorSousa, Sérgio
dc.contributor.advisorFerraz, Ricardo
dc.contributor.authorOliveira, Tiago André Cunha
dc.date.accessioned2024-01-29T12:27:48Z
dc.date.embargo2026-11-22
dc.date.issued2023-11-22
dc.description.abstractCongenital 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.
dc.identifier.tid203472993pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.22/24780
dc.language.isoengpt_PT
dc.relationDissertation realized with the support from FCT - Fundação para a Ciência e Tecnologia (Portuguese national funding agency for science, research, and technology) under the project UIDP/04378/2020 through UCIBIO - Applied Molecular Biosciences Unit/REQUIMTE (Rede de Química e Tecnologia). This work was also supported by INCD funded by FCT and FEDER under the project 01/SAICT/2016 number 022153pt_PT
dc.subjectComputacional methodspt_PT
dc.subjectMolecular dynamicspt_PT
dc.subjectGenotype-phenotype correlationpt_PT
dc.subjectPMM2pt_PT
dc.subjectPMM2-CDGpt_PT
dc.titleUnderstanding the molecular bases behind congenital disorders of glycosylationpt_PT
dc.typemaster thesis
dspace.entity.typePublication
rcaap.rightsembargoedAccesspt_PT
rcaap.typemasterThesispt_PT
thesis.degree.nameBioquímica em Saúdept_PT

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