Theses & Book Chapters
- Litou, Z., Baltoumas, F., Iconomidou, V. (2019) An introduction to the Unix and Linux Operating systems. Chapter 1 in Bioinformatics Lab Coursebook. Department of Biology, National & Kapodistrian University of Athens, Athens, Greece. [PDF] (in Greek)
Description: An introductory guide to using the Unix and Linux operating systems, targeted towards beginners, and Biologists in particular. It outlines the main features of the Unix filesystem and a comprehensive presentation of major Linux terminal functions, accompanied by examples.
- Baltoumas, F.A. (2019) Computational Studies of Protein-Protein Interactions in Transmembrane Proteins. PhD Thesis. Department of Biology, National & Kapodistrian University of Athens, Athens, Greece.
Links: National Documentation Centre || “Pergamos” Institutional Repository, NKUA
Abstract: Biological membranes are crucial components of all cells. They are bilayer mixtures composed by various types of lipids and a large number of membrane proteins. The latter, based on their position with respect to the membrane plane, are classified into transmembrane, peripheral membrane and lipid-anchored proteins. Transmembrane proteins constitute approximately 25-30% of known proteomes and control a wide range of cell functions, ranging from signal transduction and substrate transport to maintaining cell integrity and the regulation of gene expression, cell growth and cell death. As a result, transmembrane proteins have been implicated in a wide range of diseases and constitute prime targets in drug design. An important part of transmembrane protein functionality is their capability to form protein-protein interactions. The formation of supramolecular protein-protein complexes in the membrane plane, either between two or more transmembrane proteins or between transmembrane and non-transmembrane proteins, is an integral part of their canonical function. At the same time, a large number of transmembrane protein complexes have been implicated with several diseases. Despite their importance, however, the experimental study of transmembrane proteins and their interactions is not straightforward. The aim of this dissertation is the computational study of protein-protein interactions in biological membranes and transmembrane proteins. Towards this end, an extensive study of protein – protein interactions was conducted for several transmembrane proteins, both at the structural level, through Molecular Modeling, Molecular Dynamics simulations and Free Energy calculations, and in a system-wide approach, through the application of concepts from Network Theory. Alongside protein – protein interactions, the structural and dynamic aspects of the membrane environment were also investigated, in order to identify and evaluate the structural determinants that govern the lipid bilayer’s influences upon transmembrane protein structure and biomolecular interactions. Finally, during the course of this study, a number of publicly available, computational tools were developed, which can further aid in the study of biological membranes, transmembrane proteins and their interactions. The aforementioned studies were conducted both for transmembrane proteins located at the plasma membrane of eukaryotic cells, such as G-protein coupled receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs), and for proteins found in other cell components, such as the Outer Membranes of Gram-negative bacteria and transmembrane β-barrels, as well as the double membrane system of the Nuclear Envelope and its proteins. The results of this dissertation can be applicable in the further study of protein-protein interactions in transmembrane proteins, both through experimental and through computational approaches.
- Baltoumas, F.A. (2015) Computational Studies of G-protein coupled receptor (GPCR) oligomerization Interactions. Msc Thesis. Bioinformatics Post-graduate Programme, Department of Biology, National & Kapodistrian University of Athens, Athens, Greece.
Link: “Pergamos” Institutional Repository, NKUA
Abstract: G-protein coupled receptors (GPCRs) are one of the largest and most diverse superfamilies of transmembrane receptors in eukaroytic organisms. Although they have been traditionally thought to act solely as monomers, accumulating evidence suggests that GPCRs may also form dimers and higher order oligomers. However, the structural determinants, stoichiometry and functional relevance of GPCR oligomerization remain controversial. The object of this thesis is the computational study of the structural elements that govern GPCR oligomerization. The dynamic behavior of GPCR dimers and oligomers was monitored using Molecular Dynamics simulations, macromolecular interaction analysis and the study of the above using interaction network analysis. Through the aforementioned techniques, a number of conserved structural and dynamic features were consistently observed among all analyzed GPCR complexes, suggesting a common pattern for oligomerization. Amino acid residues particpating in π-electron and polar interactions near the membrane boundaries were identified as the strongest protein-protein contacts in the complexes. Finally, the combination of Molecular Dynamics with interaction network analysis, through the method of Dynamical Network Analysis, revealed correlations between the oligomerization interface and structural segments implicated in GPCR function, indicating a potential mechanism through which oligomerization may affect receptor functionality. Overall, these results may be applicable in further studying GPCR oligomerization and transmembrane protein-protein interactions in general, as well as in the design of novel pharmaceuticals, targeting GPCR oligomers.