Structural decomposition and structural relaxation of solvation shells of hydrated molecular ionic liquids and protein solutions

Die vorliegende Arbeit liefert neue methodische Beitraege zur Untersuchung der Struktur und Dynamik von Biomolekuelen in Loesung mittels Voronoi-Analyse von Computersimulationen. Dabei werden sowohl kollektive wie auch Einteilchen-Eigenschaften der Solvathuellen und des Bulk-Mediums betrachtet. Als Modellproteine dienen Ubiquitin (PDB-code: 1UBQ), Calbindin (1CLB) und eine Phospholipase (2PLD) deren Solvatation in Wasser einen wesentlichen Bestandteil dieser Arbeit darstellt. Darueber hinaus werden Vorstudien zu Molekularen Ionischen Fluessigkeiten (MIL) angestellt die in den letzten Jahren unter anderem als umweltvertraegliche polare Loesungsmittel in den Vordergrund getreten sind. Trifluoroazetat-, Tetrafluoroborat- und Trifluoromethylsulfonat- Salze von alkyliertem Imidazolium werden einerseits in Reinform, andererseits in Mischung mit Wasser untersucht. Neu an dieser Arbeit ist zunaechst die Atom-aufgeloeste Tesselierung, die fuer Systeme mit 30000 Atomen mit periodischen Randbedingungen ueber hundertausende Zeitschritte sehr rechenintensiv, und daher nur durch die effiziente Implementierung geeigneter Algorithmen zu bewerkstelligen ist. Auf dieser Grundlage werden weitestgehend parameterfreie Ansaetze zur lokalen und globalen Strukturanalyse entwickelt die einerseits mit konventionellen Methoden wie etwa Radialen Verteilungsfunktionen und Orientierungskorrelationsfunktionen verglichen werden, andererseits zusaetzliche Moeglichkeiten der Interpretation bieten. Position und Orientierung von benachbarten Molekuelen kann direkt anhand von graphentheoretischen Interaktionen beschrieben und interpretiert werden. Ein Markov-Modell fuer die Dynamik innerhalb und zwischen einzelnen Solvathuellen wird entwickelt und auf MIL Systeme angewendet.The present work provides new methodical contributions to investigation of structural and dynamic behaviour of solvated biomolecules using Voronoi analysis of computer simulations. Thereby, collective as well as single particle properties of solvation shells and the bulk medium are considered. The three proteins ubiquitin (PDB-code: 1UBQ), calbindin (1CLB) and phospholipase (2PLD) serve as model systems. The study of their solvation in water is an integral part of this work. Moreover, preliminary studies of Molecular Ionic Liquids (MIL) are being made, that have come to the fore in recent years as environmentally compliant polar solvents. Alkylated imidazolium salts of Trifluoroacetate, Tetrafluoroborate and Trifluoromethylsulfonate are analysed in the pure form as well as mixed with water. For one thing, new in this work is the atom-resolved tesselation, that is computationally demanding for systems with about 30000 atoms and periodic boundary conditions over 100-thousands of time steps and hence is to be managed only by the efficient implementation of suitable algorithms. Widely parameter free approaches to local and global structure analysis are developed on this basis and compared to conventional methods like radial distribution functions and orientation correlation functions. Furthermore, they provide additional possibilities for interpretation. Position and orientation of neighbouring molecules can be described and interpreted directly by graph theoretical interactions. A Markov model for dynamics within and between solvation shells is being developed and applied to MIL systems

Oxygen in metabolic dysfunction and its therapeutic relevance

Significance: In recent years, a number of studies have shown altered oxygen partial pressure at a tissue level in metabolic disorders, and some researchers have considered oxygen to be a (macro) nutrient. Oxygen availability may be compromised in obesity and several other metabolism-related pathological conditions, including sleep apnea-hypopnea syndrome, the metabolic syndrome (which is a set of conditions), type 2 diabetes, cardiovascular disease and cancer. Recent Advances: Strategies designed to reduce adiposity and its accompanying disorders have been mainly centered on nutritional interventions and physical activity programs. However, novel therapies are needed since these approaches have not been sufficient to counteract the worldwide increasing rates of metabolic disorders. In this regard, intermittent hypoxia training and hyperoxia could be potential treatments through oxygen-related adaptations. Moreover, living at high altitude may have a protective effect against the development of abnormal metabolic conditions. In addition, oxygen delivery systems may be of therapeutic value for supplying the tissue-specific oxygen requirements. Critical Issues: Precise in vivo methods to measure oxygenation are vital to disentangle some of the controversies related to this research area. Furthermore, it is evident that there is a growing need for novel in vitro models to study the potential pathways involved in metabolic dysfunction in order to find appropriate therapeutic targets. Future directions: Based on the existing evidence, it is suggested that oxygen availability has a key role in obesity and related comorbidities. Oxygen should be considered in relation to potential therapeutic strategies in the treatment and prevention of metabolic disorders