Membrane Protein Stability Analyses by Means of Protein Energy Profiles in Case of Nephrogenic Diabetes Insipidus

Diabetes insipidus (DI) is a rare endocrine, inheritable disorder with low incidences in an estimated one per 25,000–30,000 live births. This disease is characterized by polyuria and compensatory polydypsia. The diverse underlying causes of DI can be central defects, in which no functional arginine vasopressin (AVP) is released from the pituitary or can be a result of defects in the kidney (nephrogenic DI, NDI). NDI is a disorder in which patients are unable to concentrate their urine despite the presence of AVP. This antidiuretic hormone regulates the process of water reabsorption from the prourine that is formed in the kidney. It binds to its type-2 receptor (V2R) in the kidney induces a cAMP-driven cascade, which leads to the insertion of aquaporin-2 water channels into the apical membrane. Mutations in the genes of V2R and aquaporin-2 often lead to NDI. We investigated a structure model of V2R in its bound and unbound state regarding protein stability using a novel protein energy profile approach. Furthermore, these techniques were applied to the wild-type and selected mutations of aquaporin-2. We show that our results correspond well to experimental water ux analysis, which confirms the applicability of our theoretical approach to equivalent problems

A multiscale model of the regulation of aquaporin 2 recycling

The response of cells to their environment is driven by a variety of proteins and messenger molecules. In eukaryotes, their distribution and location in the cell are regulated by the vesicular transport system. The transport of aquaporin 2 between membrane and storage region is a crucial part of the water reabsorption in renal principal cells, and its malfunction can lead to Diabetes insipidus. To understand the regulation of this system, we aggregated pathways and mechanisms from literature and derived three models in a hypothesis-driven approach. Furthermore, we combined the models to a single system to gain insight into key regulatory mechanisms of Aquaporin 2 recycling. To achieve this, we developed a multiscale computational framework for the modeling and simulation of cellular systems. The analysis of the system rationalizes that the compartmentalization of cAMP in renal principal cells is a result of the protein kinase A signalosome and can only occur if specific cellular components are observed in conjunction. Endocytotic and exocytotic processes are inherently connected and can be regulated by the same protein kinase A signal

Symposium „Digital bis ins Mark?!“ Digitaler Wandel in der Anthropologie und im Umgang mit Sammlungen - Synergien zwischen den Wissenschaften und Technologien

Die Publikation enthält die Abstracts der wissenschaftlichen Beiträge (Präsentationen) sowie weitere Dokumentation des Online-Symposiums „Digital bis ins Mark?!“ vom 18.03.2021

Forensic Analysis of Bloodstain Color

This book chapter delves into the field of colorimetric analysis of bloodstains in forensic science, focusing on its application in crime scene investigation. Therefore it provides a comprehensive overview of the biological background of age-induced color changes. The chapter begins with an introduction to the significance of blood evidence in solving crimes and the emergence of colorimetry as a valuable tool in blood analysis. The principles of forensic spectroscopy are explored, specifically its ability to provide information crucial to crime reconstruction, such as the age of bloodstains. The chapter discusses the transformation of hemoglobin derivatives over time and the corresponding measurable color changes that accompany aging blood traces

2Statistically significant dependence of the Xaa-Pro peptide bond conformation on secondary structure and amino acid sequence

BACKGROUND: A reliable prediction of the Xaa-Pro peptide bond conformation would be a useful tool for many protein structure calculation methods. We have analyzed the Protein Data Bank and show that the combined use of sequential and structural information has a predictive value for the assessment of the cis versus trans peptide bond conformation of Xaa-Pro within proteins. For the analysis of the data sets different statistical methods such as the calculation of the Chou-Fasman parameters and occurrence matrices were used. Furthermore we analyzed the relationship between the relative solvent accessibility and the relative occurrence of prolines in the cis and in the trans conformation. RESULTS: One of the main results of the statistical investigations is the ranking of the secondary structure and sequence information with respect to the prediction of the Xaa-Pro peptide bond conformation. We observed a significant impact of secondary structure information on the occurrence of the Xaa-Pro peptide bond conformation, while the sequence information of amino acids neighboring proline is of little predictive value for the conformation of this bond. CONCLUSION: In this work, we present an extensive analysis of the occurrence of the cis and trans proline conformation in proteins. Based on the data set, we derived patterns and rules for a possible prediction of the proline conformation. Upon adoption of the Chou-Fasman parameters, we are able to derive statistically relevant correlations between the secondary structure of amino acid fragments and the Xaa-Pro peptide bond conformation

The observation of evolutionary interaction pattern pairs in membrane proteins

BACKGROUND: Over the last two decades, many approaches have been developed in bioinformatics that aim at one of the most promising, yet unsolved problems in modern life sciences - prediction of structural features of a protein. Such tasks addressed to transmembrane protein structures provide valuable knowledge about their three-dimensional structure. For this reason, the analysis of membrane proteins is essential in genomic and proteomic-wide investigations. Thus, many in-silico approaches have been utilized extensively to gain crucial advances in understanding membrane protein structures and functions. RESULTS: It turned out that amino acid covariation within interacting sequence parts, extracted from a evolutionary sequence record of α-helical membrane proteins, can be used for structure prediction. In a recent study we discussed the significance of short membrane sequence motifs widely present in nature that act as stabilizing ’building blocks’ during protein folding and in retaining the three-dimensional fold. In this work, we used motif data to define evolutionary interaction pattern pairs. These were obtained from different pattern alignments and were used to evaluate which coupling mechanisms the evolution provides. It can be shown that short interaction patterns of homologous sequence records are membrane protein family-specific signatures. These signatures can provide valuable information for structure prediction and protein classification. The results indicate a good agreement with recent studies. CONCLUSIONS: Generally, it can be shown how the evolution contributes to realize covariation within discriminative interaction patterns to maintain structure and function. This points to their general importance for α-helical membrane protein structure formation and interaction mediation. In the process, no fundamentally energetic approaches of previous published works are considered. The low-cost rapid computational methods postulated in this work provides valuable information to classify unknown α-helical transmembrane proteins and to determine their structural similarity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12900-015-0033-5) contains supplementary material, which is available to authorized users

Clusterbildung in finiten und expandierenden Systemen

Diese Promotionsarbeit liefert Beiträge zur Nukleationstheorie. Der Prozess der Clusterung von Wassermolekülen in einem finiten übersättigten Wasserdampf wird mittels Mastergleichungformalismus beschrieben. Es erfolgt eine Erweiterung der Beschreibung auf offene expandierende Systeme, wobei ein Teilchenaustausch mit der Umgebeung stattfindet. Ansätze für die Bindungsenergie von Clustern werden getestet

New Strategies for Evaluation and Analysis of SELEX Experiments

Aptamers are an interesting alternative to antibodies in pharmaceutics and biosensorics, because they are able to bind to a multitude of possible target molecules with high affinity. Therefore the process of finding such aptamers, which is commonly a SELEX screening process, becomes crucial. The standard SELEX procedure schedules the validation of certain found aptamers via binding experiments, which is not leading to any detailed specification of the aptamer enrichment during the screening. For the purpose of advanced analysis of the accrued enrichment within the SELEX library we used sequence information gathered by next generation sequencing techniques in addition to the standard SELEX procedure. As sequence motifs are one possibility of enrichment description, the need of finding those recurring sequence motifs corresponding to substructures within the aptamers, which are characteristically fitted to specific binding sites of the target, arises. In this paper a motif search algorithm is presented, which helps to describe the aptamers enrichment in more detail. The extensive characterization of target and binding aptamers may later reveal a functional connection between these molecules, which can be modeled and used to optimize future SELEX runs in case of the generation of target-specific starting libraries.</jats:p