A5065315364- Spectroscopy and Quantum Chemical Studies
- Protein Structure and Dynamics
- RNA and protein synthesis mechanisms
- Lipid Membrane Structure and Behavior
- Electrostatics and Colloid Interactions
- DNA and Nucleic Acid Chemistry
- Force Microscopy Techniques and Applications
- Alzheimer's disease research and treatments
- Nanopore and Nanochannel Transport Studies
- Material Dynamics and Properties
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Bacteriophages and microbial interactions
- Supramolecular Self-Assembly in Materials
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Advanced NMR Techniques and Applications
- Prion Diseases and Protein Misfolding
- Pickering emulsions and particle stabilization
- Surfactants and Colloidal Systems
- Ion-surface interactions and analysis
- Phase Equilibria and Thermodynamics
- Nuclear Structure and Function
- Hydrogen Storage and Materials
- Polymer Surface Interaction Studies
- Membrane-based Ion Separation Techniques
University of Augsburg
2022-2025
Max Planck Institute of Biophysics
2016-2023
University of California, Berkeley
2014-2016
University of Konstanz
2009-2013
Technical University of Munich
2009-2013
Freie Universität Berlin
2012-2013
We describe a two-scale modeling approach toward anion specificity at surfaces of varying charge and polarity. Explicit-solvent atomistic molecular dynamics simulations neutral hydrophobic (i.e., nonpolar) hydrophilic polar) self-assembled monolayers furnish potentials mean force for Na+ the halide anions F−, Cl−, I− which are then used within Poisson−Boltzmann theory to calculate ionic distributions arbitrary finite ion concentration. On basis calculated long-ranged electrostatic forces...
Using a two-step modeling approach, we address the full spectrum of direct, reversed, and altered ionic sequences as charge ion, surface, surface polarity are varied. From solvent-explicit molecular dynamics simulations, extract single-ion interaction potentials for halide alkali ions at hydrophilic hydrophobic surfaces. These used within Poisson–Boltzmann theory to calculate ion density electrostatic potential distributions mixed polar/unpolar surfaces varying charge. The resulting...
Metal cations are essential in many vital processes. In order to capture the role of different all-atom molecular dynamics simulations biological processes, an accurate parametrization is crucial. Here, we develop force field parameters for metal Li+, Na+, K+, Cs+, Mg2+, Ca2+, Sr2+, and Ba2+ combination with TIP3P water model that frequently used biomolecular simulations. progressing toward improved fields, approach presented here extension previous efforts allows us simultaneously reproduce...
Magnesium ions play an essential role in many vital processes. To correctly describe their interactions molecular dynamics simulations, accurate parametrization is crucial. Despite the importance and considerable scientific effort, current force fields based on commonly used 12–6 Lennard-Jones interaction potential fail to reproduce a variety of experimental solution properties. In particular, no exists so far that simultaneously reproduces solvation free energy distance water oxygens first...
Abstract The structure and properties of DNA depend on the environment, in particular ion atmosphere. Here, we investigate how twist -one central DNA- changes with concentration identity surrounding ions. To resolve cations influence twist, combine single-molecule magnetic tweezer experiments extensive all-atom molecular dynamics simulations. Two interconnected trends are observed for monovalent alkali divalent alkaline earth cations. First, increases monotonously increasing all ions...
Lipid nanoparticles (LNPs) are advanced core-shell particles for messenger RNA (mRNA) based therapies that made of polyethylene glycol (PEG) lipid, distearoylphosphatidylcholine (DSPC), cationic ionizable lipid (CIL), cholesterol (chol), and mRNA. Yet the mechanism pH-dependent response is believed to cause endosomal release LNPs not well understood. Here, we show eGFP (enhanced green fluorescent protein) protein expression in mouse liver mediated by lipids DLin-MC3-DMA (MC3), DLin-KC2-DMA...
Filamentous β-amyloid aggregates are crucial for the pathology of Alzheimer's disease. Despite tremendous biomedical importance, molecular pathway growth propagation is not completely understood and remains challenging to investigate by simulations due long time scales involved. Here, we apply extensive all-atom dynamics in explicit water obtain free energy profiles kinetic information from position-dependent diffusion three different Aβ9-40-growth processes: fibril elongation single...
The force-induced desorption of single peptide chains from mixed OH/CH3-terminated self-assembled monolayers is studied in closely matched molecular dynamics simulations and atomic force microscopy experiments with the goal to gain microscopic understanding transition between adsorption resistance as surface contact angle varied. In both experiments, surfaces become resistant against hydrophilic well hydrophobic peptides when their decreases below θ ≈ 50°–60°, thus confirming so-called Berg...
Ion binding to acidic groups is a central mechanism for ion-specificity of macromolecules and surfaces. Depending on pH, are either protonated or deprotonated thus change not only charge but also chemical structure with crucial implications their interaction ions. In two-step modeling approach, we first determine single-ion surface potentials few selected halide alkali ions at uncharged carboxyl (COOH) charged carboxylate (COO–) from atomistic MD simulations explicit water. Care taken...
Hydration forces play a crucial role in wide range of phenomena physics, chemistry, and biology. Here, we study the hydration mica surfaces contact with various alkali chloride solutions over concentrations pH values. Using atomic force microscopy molecular dynamics simulations, demonstrate that consist superposition monotonically decaying an oscillatory part, each unique dependence on specific type cation. The monotonic gradually decreases strength decreasing bulk energy, leading to...
A large variety of physicochemical properties involving RNA depends on the type metal cation present in solution. In order to gain microscopic insight into origin these ion specific effects, we apply molecular dynamics simulations describe interactions cations and RNA. For three most common binding sites RNA, calculate affinities exchange rates eight different mono- divalent cations. Our results reveal that phosphate groups preferentially bind with high charge density (such as Mg2+)...
Water exchange between the coordination shells of metal cations in aqueous solutions is fundamental understanding their role biochemical processes. Despite importance, microscopic mechanism water first hydration shell Mg2+ has not been resolved since dynamics out reach for conventional all-atom simulations. To overcome this challenge, transition path sampling applied to resolve kinetic pathways, characterize reaction and provide an accurate estimate rate. The results reveal that involves...
Magnesium and calcium play an essential role in the folding function of nucleic acids. To correctly describe their interactions with DNA RNA biomolecular simulations, accurate parameterization is crucial. In most cases, ion parameters are optimized based on a set experimental solution properties such as solvation free energies, radial distribution functions, water exchange rates, activity coefficient derivatives. However, transferability bulk-optimized to quantitatively systems limited....
Abstract Several studies showed that seeding of solutions monomeric fibril proteins with ex vivo amyloid fibrils accelerated the kinetics formation in vitro but did not necessarily replicate seed structure. In this research we use cryo-electron microscopy and other methods to analyze ability serum A (SAA)1.1-derived fibrils, purified from systemic AA amyloidosis tissue, recombinant SAA1.1 protein. We show 98% seeded remodel full structure main morphology, which used for seeding, while they...
Lipid nanoparticles (LNPs) are efficient and safe carriers for mRNA vaccines based on advanced ionizable lipids. It is understood that the pH dependent structural transition of mesoscopic LNP core phase plays a key role in transfer. However, buffer specific variations transfection efficiency remain obscure. Here we analyze effect type structure LNPs. We find LNPs formulated with cationic lipid DLin-MC3-DMA (MC3) citrate compared to phosphate acetate buffers exhibit earlier onset stronger...
Oligoadenylate synthetase (OAS) proteins are immune sensors for double-stranded RNA and critical restricting viruses. OAS2 comprises two OAS domains, only one of which can synthesize 2'-5'-oligoadenylates RNase L activation. Existing structures OAS1 provide a model enzyme activation, but do not explain how multiple domains discriminate length. Here, we discover that exists in an autoinhibited state as zinc-mediated dimer present mechanism length discrimination: the catalytically deficient...
Lipid nanoparticles (LNPs) are efficient and safe carriers for mRNA vaccines based on advanced ionizable lipids. It is understood that the pH-dependent structural transition of mesoscopic LNP core phase plays a key role in transfer. However, buffer-specific variations transfection efficiency remain obscure. Here we analyze effect buffer type LNPs. We find LNPs formulated with cationic lipids DLin-MC3-DMA (MC3), SM-102, ALC-315 citrate compared to phosphate acetate buffers exhibit earlier...
The distribution of cations around nucleic acids is essential for a broad variety processes ranging from DNA condensation and RNA folding to the detection biomolecules in biosensors. Predicting exact ions remains challenging since and, hence, acid properties depend on salt concentration, valency ions, ion type. Despite importance, general theory quantify ion-specific effects highly charged still lacking. Moreover, recent experiments reveal that despite their similar building blocks, duplexes...
Aβ amyloid fibrils from Alzheimer's brain tissue are polymorphic and structurally different typical in vitro formed fibrils. Here, we show that brain-derived (ex vivo) fibril structures can be proliferated by seeding vitro. The proliferation reaction is only efficient for one of the three abundant ex vivo morphologies, which consists two peptide stacks, while inefficiently morphologies contain four or six stacks. In addition to seeded structures, find de novo nucleated emerge samples if...
The diffusion behavior of interacting particles determines the a large number systems ranging from pedestrians crossing road to ions passing through channels in living cells. Here we present system which nature process varies with changes external conditions. We find this special colloidal model system, consisting micron sized are confined narrow and interact via induced magnetic dipoles. When density these is changed, alternates between normal Fickian single-file diffusion. This anomalous...
Secondary nucleation pathways in which existing amyloid fibrils catalyze the formation of new aggregates and neurotoxic oligomers are immediate importance for onset progression Alzheimer's disease. Here, we apply extensive all-atom molecular dynamics simulations explicit water to study surface-activated secondary at extended lateral β-sheet surface a preformed Aβ9-40 filament. Calculation free-energy profiles allows us determine binding free energies conformational intermediates complexes...
Magnesium is essential in many vital processes. To correctly describe Mg2+ physiological processes by molecular dynamics simulations, accurate force fields are fundamental. Despite the importance, based on commonly used 12-6 Lennard-Jones potential showed significant shortcomings. Recently progress was made an optimization procedure that implicitly accounts for polarizability. The resulting microMg and nanoMg (J. Chem. Theory Comput. 2021, 17, 2530–2540) accurately reproduce a broad range of...
Force fields for Dlin-MC3-DMA lipids molecular dynamics simulations validated by structural insights from neutron reflectivity experiments.
Magnesium plays a vital role in large variety of biological processes. To model such processes by molecular dynamics simulations, researchers rely on accurate force field parameters for Mg2+ and water. OPC is one the most promising water models yielding an improved description biomolecules The aim this work to provide that lead simulation results combination with Using 12 different parameter sets were previously optimized models, we systematically assess transferability based experimental...