ITQB: PM - PhD Theses
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- Unlocking Viral Entry: The Key Role of Fusion ProteinsPublication . de Oliveira Farinha Fidalgo Valério, Mariana; Soares, Cláudio M.; Lousa, Diana; Melo, Manuel"Viral infections are a substantial global health concern, affecting millions of individuals annually. The initial stage of infection involves viral entry, a process characterized by intricate mechanisms that remain poorly understood. In this thesis, we employ molecular dynamics simulations to elucidate the complex mechanisms that allow for the entry of enveloped viruses into our cells. To achieve this we focused on the existing gaps in the literature concerning the role of fusion proteins in ensuring efficient viral infection, with specific attention directed towards events associated with target cell receptor recognition and membrane fusion. This was studied by analyzing both the SARS-CoV-2 and parainfluenza 5 viruses.(...)"
- Studies on the function and substrate permeation in ABC transporters by biomolecular simulations.Publication . Pinto, Bárbara Palma de Abreu Caldeira; Soares, Cláudio; Oliveira, Ana Sofia"The translocation of molecules across cell membranes often requires the participation of transmembrane proteins. The ATP Binding Cassette (ABC) transporters are one of the major class of proteins dedicated to the translocation of molecules across membranes. ABC transporters make use of ATP hydrolysis and undergo a series of large-scale conformational changes in order to carry out their function. Despite being extensively studied, some molecular details regarding their function remain undisclosed. In this thesis, the function of three relevant ABC systems, CFTR, MsbA and the Escherichia coli MalFGK2E importer, was investigated using computational methods, such as molecular dynamics simulations. The effect of the CFTR mutation F508del, responsible for cystic fibrosis, was studied in the nucleotide binding domains of the CFTR receptor. In the MsbA protein, the molecular details of nucleotide binding during the adenylate kinase cycle were investigated in collaboration with experimental groups with expertise in solid state NMR and EPR. Finally, the details of substrate translocation in the MalFGK2E importer were also researched.(...)"
- Molecular determinants of nonaqueous biocatalysisPublication . Lousa, Diana Pereira; Soares,Cláudio M.; Baptista, António M.Over the last thirty years, the tremendous biotechnological potential of nonaqueous biocatalysis has boosted research efforts in this area. Numerous studies have tried to elucidate how enzymes work in these nonconventional media and many properties are now well understood. However, when this thesis was initiated, some aspects of this field were poorly characterized at the molecular level. In particular, the molecular determinants of protein-ion interactions, enzyme stability, and molecular memory, are important issues which were lacking a thorough molecular analysis. These three subjects are herein investigated using molecular simulation methodologies.(...)
- Molecular modelling of ABC transporters: from ATP hydrolysis to substrate transportPublication . Oliveira, Ana Sofia Fernandes; Soares, Cláudio M.Despite the great advances that have been made in the past decades in the ABC transporters field, the molecular mechanisms involved in transport across membranes remains largely an enigma. To date, questions regarding the molecular mechanism of transport, nucleotide hydrolysis and inorganic phosphate exit from the binding sites are still unanswered. In this thesis the dynamic behavior of several ABC transporters during the ATP-hydrolytic cycle is investigated using molecular modeling methods. The content of this thesis is compiled in three main scientific publications [1-3], corresponding to sections 3, 4 and 5, respectively. Although these three works are performed in prokaryotic family ABC transporters, it is likely that eukaryotic ones use similar mechanisms for nucleotide hydrolysis, inter-domain communication and allocrite translocation.(...)