A5026501395- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Gene Regulatory Network Analysis
- Spectroscopy and Quantum Chemical Studies
- Markov Chains and Monte Carlo Methods
- Mass Spectrometry Techniques and Applications
- Advanced Thermodynamics and Statistical Mechanics
- Receptor Mechanisms and Signaling
- Analytical Chemistry and Chromatography
- Advanced Chemical Physics Studies
- Theoretical and Computational Physics
- Model Reduction and Neural Networks
- Machine Learning in Materials Science
- Neuropeptides and Animal Physiology
- Bioinformatics and Genomic Networks
- Monoclonal and Polyclonal Antibodies Research
- Scientific Computing and Data Management
- Stochastic processes and statistical mechanics
- Estrogen and related hormone effects
- Molecular spectroscopy and chirality
- stochastic dynamics and bifurcation
- Advanced biosensing and bioanalysis techniques
- Quantum chaos and dynamical systems
- Enzyme Structure and Function
- Graph theory and applications
Zuse Institute Berlin
2016-2025
Kantonsspital St. Gallen
2023
Freie Universität Berlin
2007-2017
Stanford University
2017
Helios Dr. Horst Schmidt Kliniken Wiesbaden
2014
Technische Universität Braunschweig
2014
University of Rostock
2010
Merseburg University of Applied Sciences
1987
Abstract Multivalent interactions can be applied universally for a targeted strengthening of an interaction between different interfaces or molecules. The binding partners form cooperative, multiple receptor–ligand that are based on individually weak, noncovalent bonds and thus generally reversible. Hence, multi‐ polyvalent play decisive role in biological systems recognition, adhesion, signal processes. scientific practical realization this principle will demonstrated by the development...
A pain killer without side effects Opioids are very strong and effective killers. However, they also have a range of well-known can cause addiction. Painful conditions such as inflammation or trauma often associated with localized tissue acidification. Spahn et al. designed novel opioid receptor agonist that, unlike clinically used opioids, best activates the receptors in acidified tissues. In rat models inflammatory pain, new drug exerted relief essentially standard opioids. Science , this...
Abstract Multivalente Wechselwirkungen können universell zur gezielten Bindungsverstärkung zwischen verschiedenen Grenzflächen oder Molekülen genutzt werden. Die Bindungspartner bilden dabei kooperativ multiple Rezeptor‐Ligand‐Wechselwirkungen, die auf einzelnen schwachen, nichtkovalenten Bindungen basieren und daher prinzipiell reversibel sind. Daher spielen multi‐ polyvalente in biologischen Systemen eine entscheidende Rolle für Erkennungs‐, Adhäsions‐ Signalprozesse. wissenschaftliche...
The coarse graining method to be advocated in this paper consists of two main steps. First, the propagation an ensemble molecular states is described as a Markov chain by transition probability matrix finite state space. Second, we obtain metastable conformations aggregation variables via Robust Perron Cluster Analysis (PCCA+). Up now, it has been open question how space can transformed while preserving essential dynamic information. In article, construct that correct propagator...
A wide range of multivalent scaffolds was assembled by using only five different PNA oligomers and various DNA templates. The flexibility the PNA–DNA duplexes could be increased introducing nick-sites partially unpaired regions, as confirmed MD simulations. self-organized glyco-assemblies were used in a spatial screening accessible carbohydrate binding sites Erythrina cristagalli lectin (ECL). This systematic investigation revealed distance dependence which is agreement with crystal...
Molecular ruler: Steroid analogues were conjugated to DNA by using click chemistry, and self-assembly provided ternary complexes with bivalent ligand presentation. The distance between the bound ligands was measured spatial screening of estrogen receptor, a second hydrophobic binding site postulated. picture shows DNA(black)–raloxifene(orange) complex in domain receptor. Detailed facts importance specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but...
We study the cross-entropy method for diffusions. One of results is a versatile algorithm that can be used to design efficient importance sampling strategies rare events or solve optimal control problems. The approach based on minimization suitable functional, with parametric family exponentially tilted probability distributions. illustrate new several numerical examples and discuss algorithmic issues possible extensions method.
Novel pain killers without adverse effects are urgently needed. Opioids induce central and intestinal side such as respiratory depression, sedation, addiction, constipation. We have recently shown that a newly designed agonist with reduced acid dissociation constant (pKa) abolished by selectively activating peripheral μ-opioid receptors (MOR) in inflamed (acidic) tissues eliciting effects. Here, we extended this concept pKa reduction to 7.22 was achieved placing fluorine atom at the...
In 2021, the Deutsche Gesellschaft für Neurology published a new guideline on diagnosis and therapy of motor neuron disorders. Motor disorders affect upper neurons in primary cortex and/or lower brain stem spinal cord. The most frequent disease amyotrophic lateral sclerosis (ALS) is rapidly progressive with an average life expectancy 2-4 years yearly incidence 3.1/100,000 Central Europe (Rosenbohm et al. J Neurol 264(4):749-757, 2017. https://doi.org/10.1007/s00415-017-8413-3 ). It...
Multivalent ligand-receptor systems often show an enhancement in binding compared to the constituent monovalent systems. This “cooperativity effect” is attributed favorable spatial preorganisation of ligands by connecting spacer that leads a reduction entropy loss at ligand binding. A different factor has been proposed contribute cooperativity effect “rebinding”: As soon as single complex dissociates, presence another “on coat-tails” will increase probability event, which turn drive system...
Markov state models (MSMs) have received an unabated increase in popularity recent years, as they are very well suited for the identification and analysis of metastable states related kinetics. However, state-of-the-art modeling methods tools enforce fulfillment a detailed balance condition, restricting their applicability to equilibrium MSMs. To date, unsuitable deal with general dominant data structures including cyclic processes, which essentially associated nonequilibrium systems....
Markov state models are to date the gold standard for modeling molecular kinetics since they enable identification and analysis of metastable states related in a very instructive manner. The state-of-the-art methods tools well developed reversible processes closed equilibrium systems. On contrary, largely not suited deal with nonreversible or even nonautonomous nonequilibrium Thus, we generalized common Robust Perron Cluster Analysis (PCCA+) method straightforward systems as well. resulting...
Abstract A series of precision glycomacromolecules is prepared following previously established solid phase synthesis allowing for controlled variations interligand spacing and the overall number carbohydrate ligands. In addition, now also different linkers are installed between ligand macromolecular scaffold. The lectin binding behavior these then evaluated in isothermal titration calorimetry (ITC) kinITC experiments using Concanavalin (Con A) its dimeric tetrameric form. results indicate...
Trajectory- or mesh-based methods for analyzing the dynamical behavior of large molecules tend to be impractical due curse dimensionality---their computational cost increases exponentially with size molecule. We propose a method break by novel square root approximation transition rates, Monte Carlo quadrature and discretization approach based on solving linear programs. With randomly sampled points molecular energy landscape generated discretizations configuration space as our initial data,...
Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition the small GTPase RhoA and enrichment water channel aquaporin-2 (AQP2) plasma membrane. The membrane insertion facilitates reabsorption from primary urine fine-tuning body homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact RhoA, catalyze GDP for GTP thereby activate GTPase. However, GEFs involved control AQP2 are unknown. A-kinase anchoring...
Abstract The non-selective activation of central and peripheral opioid receptors is a major shortcoming currently available opioids. Targeting promising strategy to preclude side effects. Recently, we showed that fentanyl-derived μ-opioid receptor (MOR) agonists with reduced acid dissociation constants (pK ) due introducing single fluorine atoms produced injury-restricted antinociception in rat models inflammatory, postoperative neuropathic pain. Here, report new double-fluorinated compound...
O presente estudo realizou uma revisão narrativa sobre lesões no tênis, abordando sua epidemiologia, fatores de risco e principais acometimentos musculoesqueléticos. Foram analisados estudos transversais, meta-análises relatos caso, obtidos na base dados PubMed, abrangendo publicações entre 2020 2024. Os resultados indicam que as são frequentes em tenistas diferentes níveis, sendo mais comuns atletas profissionais do sexo masculino. As articulações afetadas incluem ombros, cotovelos, punhos,...
Abstract Background The dynamics of many gene regulatory networks (GRNs) is characterized by the occurrence metastable phenotypes and stochastic phenotype switches. chemical master equation (CME) most accurate description to model such dynamics, whereby long-time system encoded in spectral properties CME operator. Markov State Models (MSMs) provide a general framework for analyzing visualizing multistability state transitions based on these properties. Until now, however, this approach...