A5087602254- Protein Structure and Dynamics
- Advanced Proteomics Techniques and Applications
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Microbial Metabolic Engineering and Bioproduction
- Fungal and yeast genetics research
- COVID-19 diagnosis using AI
- Enzyme Structure and Function
- Spectroscopy and Quantum Chemical Studies
- Photosynthetic Processes and Mechanisms
- Diabetes and associated disorders
- Computational Drug Discovery Methods
- Biofuel production and bioconversion
- Bacteriophages and microbial interactions
- RNA and protein synthesis mechanisms
- SARS-CoV-2 detection and testing
- Bioinformatics and Genomic Networks
- Poxvirus research and outbreaks
- Polyamine Metabolism and Applications
- Antimicrobial Peptides and Activities
- Adipokines, Inflammation, and Metabolic Diseases
- Sepsis Diagnosis and Treatment
- Safety Systems Engineering in Autonomy
- Advanced Clustering Algorithms Research
- Click Chemistry and Applications
Charité - Universitätsmedizin Berlin
2020-2024
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2024
The Francis Crick Institute
2022
Freie Universität Berlin
2016-2022
Humboldt-Universität zu Berlin
2021-2022
COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of disease 139 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts enzyme activities, well untargeted plasma proteomes at 687 sampling points. report an initial spike a systemic inflammatory response, which gradually alleviated followed protein signature indicative tissue repair,...
Functional genomic strategies have become fundamental for annotating gene function and regulatory networks. Here, we combined functional genomics with proteomics by quantifying protein abundances in a genome-scale knockout library Saccharomyces cerevisiae, using data-independent acquisition mass spectrometry. We find that global expression is driven complex interplay of (1) general biological properties, including translation rate, turnover, the formation complexes, growth genome...
Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such SOFA APACHE II scores show only limited performance for predicting survival severely ill patients. Additional tools also needed monitor treatment, including experimental therapies clinical trials. Comprehensively capturing human physiology, we speculated that proteomics combination with new...
The core-set approach is a discretization method for Markov state models of complex molecular dynamics. Core sets are disjoint metastable regions in the conformational space, which need to be known prior construction model. We propose use density-based cluster algorithms identify cores. compare three different algorithms: CNN, DBSCAN, and Jarvis-Patrick algorithm. While based on CNN DBSCAN clustering well-converged, constructing cannot recommended. In well-converged model, number core up an...
Cyclization and selected backbone N-methylations are found to be often necessary but not sufficient conditions for peptidic drugs have a good bioavailability. Thus, the design of cyclic peptides with passive membrane permeability solubility remains challenge. The scaffold recently published series decapeptides six was designed favor adoption closed conformation β-turns four transannular hydrogen bonds. Although this indeed adopted by as determined NMR measurements, substantial differences in...
BackgroundGlobal healthcare systems continue to be challenged by the COVID-19 pandemic, and there is a need for clinical assays that can help optimise resource allocation, support treatment decisions, accelerate development evaluation of new therapies.MethodsWe developed multiplexed proteomics assay determining disease severity prognosis in COVID-19. The quantifies up 50 peptides, derived from 30 known newly introduced COVID-19-related protein markers, single measurement using routine-lab...
Report28 September 2022Open Access Transparent process The human host response to monkeypox infection: a proteomic case series study Ziyue Wang orcid.org/0000-0002-4121-4799 Department of Biochemistry, Charité – Universitätsmedizin Berlin, Germany Contribution: Formal analysis, Visualization, Methodology, Writing - original draft, review & editing Search for more papers by this author Pinkus Tober-Lau orcid.org/0000-0002-9148-3663 Infectious Diseases and Respiratory Medicine, Data curation,...
The broad substrate tolerance of tubulin tyrosine ligase enables its wide applicability for protein functionalization.
Abstract Context Humans respond profoundly to changes in diet, while nutrition and environment have a great impact on population health. It is therefore important deeply characterize the human nutritional responses. Objective Endocrine parameters metabolome of plasma are rapidly responding acute interventions such as caloric restriction or glucose challenge. less well understood whether proteome would be equally dynamic, it could source corresponding biomarkers. Methods We used...
Summary Metal ions play crucial roles in cells, yet the broader impact of metal availability on biological networks remains underexplored. We generated genome-wide resources, systematically quantifying yeast cell growth, metallomic, proteomic, and genetic responses upon varying each its essential (Ca, Cu, Fe, K, Mg, Mn, Mo, Na, Zn), over several orders magnitude. find that deeply cellular networks, with 57.6% proteome, including most signalling pathways, responding. While response to is...
Cluster analyses are often conducted with the goal to characterize an underlying probability density, for which data-point density serves as estimate this density. We here test and benchmark common nearest neighbor (CNN) cluster algorithm. This algorithm assigns a spherical neighborhood R each data point estimates between two points number of N in overlapping region their neighborhoods (step 1). The main principle CNN is growing. grows clusters by sequentially adding thereby effectively...
Many drugs that are applied in anticancer therapy such as the anthracycline doxorubicin contain DNA-intercalating 9,10-anthraquinone (AQ) moieties. When Cu(II) cyclen complexes were functionalized with up to three (2-anthraquinonyl)methyl substituents, they efficiently inhibited DNA and RNA synthesis resulting high cytotoxicity (selective for cancer cells) accompanied by condensation/aggregation phenomena. Molecular modeling suggests an unusual bisintercalation mode only one base pair...
Summary Functional genomic strategies help to address the genotype phenotype problem by annotating gene function and regulatory networks. Here, we demonstrate that combining functional genomics with proteomics uncovers general principles of protein expression, provides new avenues annotate function. We recorded precise proteomes for all non-essential knock-outs in Saccharomyces cerevisiae. find abundance is driven a complex interplay i) biological properties, including translation rate,...
Abstract COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. There an urgent need for predictive markers that can guide decision-making, inform about the effect of experimental therapies, point novel therapeutic targets. Here, we characterize time-dependent progression through different stages disease, by measuring 86 accredited diagnostic parameters plasma proteomes at 687 sampling points, a cohort 139 patients...
Abstract The functions of cells and proteins depend on their biochemical microenvironment. To understand how constraints shaped protein structural evolution, we coupled the extensive genetic metabolic data from Saccharomycotina subphylum with capability AlphaFold2 to systematically predict structures sequence. Determining 11,269 enzyme catalysing 361 different reactions evolved over 400 million years alongside molecular functions, report that metabolism has evolution enzymes at levels:...
Abstract Understanding what drives protein abundance is essential to biology, medicine, and biotechnology. Driven by evolutionary selection, the amino acid sequence tailored meet required of proteomes, underscoring intricate relationship between functional demand. Yet, specific role sequences in determining proteome remains elusive. Here, we demonstrate that predicts shaping a protein’s conformational stability. We show increasing provides metabolic cost benefits, advantage maintaining...
The assimilation, incorporation, and metabolism of sulfur is a fundamental process across all domains life, yet how cells deal with varying availability not well understood. We studied an unresolved conundrum fixation in yeast, which organosulfur auxotrophy caused by deletion the homocysteine synthase Met17p overcome when are inoculated at high cell density. In combining use self-establishing metabolically cooperating (SeMeCo) communities proteomic, genetic, biochemical approaches, we...
The water-soluble chlorophyll-binding protein (WSCP) is assumed to be not a part of the photosynthetic process. Applying molecular dynamics (MD) simulations, we aimed obtain insight into exceptional stability WSCP. We analyzed dynamical features such as hydrogen bond network, flexibility, and force distributions. WSCP structure contains two cysteines at interfaces every chain, which are in close contact with other dimer. tested if connection these between different chains influences behavior...
Abstract We introduce a Python 2.7 software called gmx2qmmm, which provides an interface between the Gaussian and Gromacs packages in additive quantum mechanics/molecular mechanics (QM/MM) scheme. Other QM will be added future releases. The main advantage of gmx2qmmm is its simplicity terms input setup configuration as it maintains file formats, well conventions. It also designed such that users do not need to reconfigure or recompile any interfaced programs. While our goal was provide...
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Abstract Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such SOFA APACHE II scores show only limited performance for predicting survival severely ill patients. Comprehensively capturing host physiology, we speculated that proteomics combination with new data-driven analysis strategies could produce generation prognostic discriminators. We studied...
Abstract Caloric restriction (CR) has proven beneficial to healthspan and lifespan, but not enough is known about the molecular mechanisms that interlink human CR response its downstream effectors. We induced acute caloric in a controlled intervention study compared plasma proteome, metabolome endocrine responses. report proteins dominate negative positive energy balance are associated with disease-relevant parameters two population studies. For example, APOC1, small understudied...
Abstract Pancreatic beta cells secrete insulin as a response to rising glucose level, process known glucose-stimulated secretion (GSIS). In this study, we used liquid chromatography tandem mass spectrometry and data-independent acquisition acquire proteomes of rat pancreatic INS-1 832/13 that were short-term stimulated with concentrations ranging from 0 20 mM, quantifying the behavior 3703 proteins across 11 concentrations. Ensemble clustering proteome profiles revealed unique patterns...
Abstract Understanding what drives protein abundance is essential to biology, medicine, and biotechnology. Driven by evolutionary selection, an amino acid sequence tailored meet the required of a proteome, underscoring intricate relationship between functional demand. Yet, specific role sequences in determining proteome remains elusive. Here we show that alone encodes over half variation across all domains life, ranging from bacteria mouse human. With attempt go beyond predictions, trained...
Abstract The assimilation, incorporation, and metabolism of sulfur is a fundamental process across all domains life, yet how cells deal with varying availability not well understood. We studied an unresolved conundrum fixation in yeast, which organosulfur-auxotrophy caused by deletion homocysteine synthase Met17p overcome when are inoculated at high cell density. discovered that uncharacterized gene YLL058Wp, herein named Hydrogen sulfide utilizing-1 ( HSU1 ), acts as allows the to...