Mining protein structure data

The principal topic of this work is the application of data mining techniques, in particular of machine learning, to the discovery of knowledge in a protein database. In the first chapter a general background is presented. Namely, in section 1.1 we overview the methodology of a Data Mining project and its main algorithms. In section 1.2 an introduction to the proteins and its supporting file formats is outlined. This chapter is concluded with section 1.3 which defines that main problem we pretend to address with this work: determine if an amino acid is exposed or buried in a protein, in a discrete way (i.e.: not continuous), for five exposition levels: 2%, 10%, 20%, 25% and 30%. In the second chapter, following closely the CRISP-DM methodology, whole the process of construction the database that supported this work is presented. Namely, it is described the process of loading data from the Protein Data Bank, DSSP and SCOP. Then an initial data exploration is performed and a simple prediction model (baseline) of the relative solvent accessibility of an amino acid is introduced. It is also introduced the Data Mining Table Creator, a program developed to produce the data mining tables required for this problem. In the third chapter the results obtained are analyzed with statistical significance tests. Initially the several used classifiers (Neural Networks, C5.0, CART and Chaid) are compared and it is concluded that C5.0 is the most suitable for the problem at stake. It is also compared the influence of parameters like the amino acid information level, the amino acid window size and the SCOP class type in the accuracy of the predictive models. The fourth chapter starts with a brief revision of the literature about amino acid relative solvent accessibility. Then, we overview the main results achieved and finally discuss about possible future work. The fifth and last chapter consists of appendices. Appendix A has the schema of the database that supported this thesis. Appendix B has a set of tables with additional information. Appendix C describes the software provided in the DVD accompanying this thesis that allows the reconstruction of the present work.

Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria

Background/Aims: Unconjugated bilirubin (UCB) impairs crucial aspects of cell function and induces apoptosis in primary cultured neurones. While mechanisms of cytotoxicity begin to unfold, mitochondria appear as potential primary targets. Methods: We used electron paramagnetic resonance spectroscopy analysis of isolated rat mitochondria to test the hypothesis that UCB physically interacts with mitochondria to induce structural membrane perturbation, leading to increased permeability, and subsequent release of apoptotic factors. Results: Our data demonstrate profound changes on mitochondrial membrane properties during incubation with UCB, including modified membrane lipid polarity and fluidity (P , 0:01), as well as disrupted protein mobility(P , 0:001). Consistent with increased permeability, cytochrome c was released from the intermembrane space(P , 0:01), perhaps uncoupling the respiratory chain and further increasing oxidative stress (P , 0:01). Both ursodeoxycholate, a mitochondrial-membrane stabilising agent, and cyclosporine A, an inhibitor of the permeability transition, almost completely abrogated UCB-induced perturbation. Conclusions: UCB directly interacts with mitochondria influencing membrane lipid and protein properties, redox status, and cytochrome c content. Thus, apoptosis induced by UCB may be mediated, at least in part, by physical perturbation of the mitochondrial membrane. These novel findings should ultimately prove useful to our evolving understanding of UCB cytotoxicity.

Localization studies of the FemXAB protein family in Staphylococcus aureus

Dissertação apresentada para a obtenção do Grau de Mestre em Genética Molecular e Biomedicina, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Production of recombinant protein hLIF in static and dynamic systems of animal cell culture

Thesis for the Degree of Master of Science in Biotechnology Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Integrating protein structural information

Dissertação apresentada para obtenção de Grau de Doutor em Bioquímica,Bioquímica Estrutural, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Protein folding, metal ions and conformational states: the case of a di-cluster ferredoxin

Dissertation presented to obtain the PhD degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Defective protein folding and function in metabolic disorders: studies on the mitochondrial flavoenzyme ETF

Dissertation presented to obtain the PhD degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Metal ions and protein folding: conformational and functional interplay

Dissertation presented to obtain a PhD degree in Biochemistry at Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Georeferencing Road Accidents with Google Earth: Transforming Information into Knowledge for Decision Support

Over the last fifty years mobility practices have changed dramatically, improving the way travel takes place, the time it takes but also on matters like road safety and prevention. High mortality caused by high accident levels has reached untenable levels. But the research into road mortality stayed limited to comparative statistical exercises which go no further than defining accident types. In terms of sharing information and mapping accidents, little progress has been mad, aside from the normal publication of figures, either through simplistic tables or web pages. With considerable technological advances on geographical information technologies, research and development stayed rather static with only a few good examples on dynamic mapping. The use of Global Positioning System (GPS) devices as normal equipments on automobile industry resulted in a more dynamic mobility patterns but also with higher degrees of uncertainty on road traffic. This paper describes a road accident georeferencing project for the Lisbon District involving fatalities and serious injuries during 2007. In the initial phase, individual information summaries were compiled giving information on accidents and its majour characteristics, collected by the security forces: the Public Safety Police Force (Polícia de Segurança Pública - PSP) and the National Guard (Guarda Nacional Republicana - GNR). The Google Earth platform was used to georeference the information in order to inform the public and the authorities of the accident locations, the nature of the location, and the causes and consequences of the accidents. This paper also gives future insights about augmented reality technologies, considered crucial to advances to road safety and prevention studies. At the end, this exercise could be considered a success because of numerous consequences, as for stakeholders who decide what to do but also for the public awareness to the problem of road mortality.

Metal ions modulate the folding and stability of the tumor suppressor protein S100A2

Febs Journal (2009)276:1776-1786

Computational design with flexible backbone sampling for protein remodeling and scaffolding of complex binding sites

Dissertation presented to obtain the Doutoramento (Ph.D.) degree in Biochemistry at the Instituto de Tecnologia Qu mica e Biol ogica da Universidade Nova de Lisboa

The Crystal Structure of the Escherichia coli Autoinducer-2 Processing Protein LsrF

PLOS ONE, 4(8):ARTe6820

Mitosis and protein Na-terminal acetylation

Dissertation presented to obtain the Ph.D degree in Developmental Biology

NMR studies of transiente protein complexes

Dissertação apresentada para obtenção do Grau de Doutor em Bioquímica,especialidade Bioquímica Física,pela Universidade Nova de Lisboa,Faculdade de Ciências e Tecnologia