A5019134059- Protein Structure and Dynamics
- Nanopore and Nanochannel Transport Studies
- Spectroscopy and Quantum Chemical Studies
- Lipid Membrane Structure and Behavior
- Advanced NMR Techniques and Applications
- Enzyme Structure and Function
- Machine Learning in Materials Science
- Gaussian Processes and Bayesian Inference
- NMR spectroscopy and applications
- Electrostatics and Colloid Interactions
- Electron Spin Resonance Studies
- Membrane-based Ion Separation Techniques
- Data Analysis with R
- Scientific Research and Discoveries
- Semantic Web and Ontologies
- Carbon Nanotubes in Composites
- Phase Equilibria and Thermodynamics
- HIV Research and Treatment
- RNA Research and Splicing
- Speech and dialogue systems
- Advanced Neuroimaging Techniques and Applications
- Stochastic processes and statistical mechanics
- Material Dynamics and Properties
- Nuclear Structure and Function
- Mass Spectrometry Techniques and Applications
Max Planck Institute of Biophysics
2015-2025
Technical University of Munich
2022
National Institute of Diabetes and Digestive and Kidney Diseases
2010-2013
National Institutes of Health
2010-2013
University of Vienna
2006-2009
The hemoprotein myoglobin is a model system for the study of protein dynamics. We used time-resolved serial femtosecond crystallography at an x-ray free-electron laser to resolve ultrafast structural changes in carbonmonoxy complex upon photolysis Fe-CO bond. Structural appear throughout within 500 femtoseconds, with C, F, and H helices moving away from heme cofactor E A toward it. These collective movements are predicted by hybrid quantum mechanics/molecular mechanics simulations. Together...
We describe different Bayesian ensemble refinement methods, examine their interrelation, and discuss practical application. With refinement, the properties of dynamic partially disordered (bio)molecular structures can be characterized by integrating a wide range experimental data, including measurements ensemble-averaged observables. start from formulation in which posterior is functional that ranks configuration space distributions. By maximizing this posterior, we derive an optimal...
Water confined into the interior channels of narrow carbon nanotubes or transmembrane proteins forms collectively oriented molecular wires held together by tight hydrogen bonds. Here, we explore thermodynamic stability and dipolar orientation such 1D water chains from nanoscopic to macroscopic dimensions. We show that a dipole lattice model accurately recovers key properties when compared atomically detailed simulations. In major reduction in computational complexity, represent terms...
Ensemble refinement produces structural ensembles of flexible and dynamic biomolecules by integrating experimental data molecular simulations. Here we present two efficient numerical methods to solve the computationally challenging maximum-entropy problem arising from a Bayesian formulation ensemble refinement. Recasting resulting constrained weight optimization into an unconstrained form enables use gradient-based algorithms. In complementary formulations that differ in their...
The paradigmatic disordered protein tau plays an important role in neuronal function and neurodegenerative diseases. To disentangle the factors controlling balance between functional disease-associated conformational states, we build a structural ensemble of K18 fragment containing four pseudorepeat domains involved both microtubule binding amyloid fibril formation. We assemble 129-residue-long chains with atomic detail from extensive library constructed molecular dynamics simulations....
Summary Upon infection, human immunodeficiency virus (HIV-1) releases its cone-shaped capsid into the cytoplasm of infected T-cells and macrophages. As largest known cargo, enters nuclear pore complex (NPC), driven by interactions with numerous FG-repeat nucleoporins (FG-Nups). Whether NPCs structurally adapt to passage whether capsids are modified during remains unknown, however. Here, we combined super-resolution correlative microscopy cryo electron tomography molecular simulations study...
Water molecules confined to pores with sub-nanometre diameters form single-file hydrogen-bonded chains. In such nanoscale confinement, water has unusual physical properties that are exploited in biology and hold promise for a wide range of biomimetic nanotechnological applications. The latter can be realized by carbon boron nitride nanotubes which confine relatively non-specific way lend themselves the study intrinsic water. As consequence strong water–water hydrogen bonds, many...
By performing molecular dynamics simulations with up to 132 million coarse-grained particles in half-micron sized boxes, we show that hydrodynamics quantitatively explains the finite-size effects on diffusion of lipids, proteins, and carbon nanotubes membranes. The resulting Oseen correction allows us extract infinite-system coefficients membrane surface viscosities from despite logarithmic divergence apparent diffusivities increasing box width. hydrodynamic theory applies also membranes...
The pair-distance distribution function (PDDF) contains all structural information probed in an elastic scattering experiment of macromolecular solutions. However, small-angle x-ray (SAXS) or neutron (SANS) experiments only their Fourier transform is measured over a restricted range angles. We therefore developed mathematically simple and computationally efficient method to calculate the PDDFs as well accurate intensities from molecular dynamics simulations. calculated solution are excellent...
Carbon nanotube porins embedded in lipid membranes are studied by molecular dynamics simulations.
Interactions among proteins, nucleic acids, and other macromolecules are essential for their biological functions shape the physicochemcial properties of crowded environments inside living cells. Binding interactions commonly quantified by dissociation constants Kd, both binding nonbinding second osmotic virial coefficients B2. As a measure nonspecific stickiness, B2 is receiving renewed attention in context so-called liquid–liquid phase separation protein acid solutions. We show that Kd...
Drug delivery mitigates toxic side effects and poor pharmacokinetics of life-saving therapeutics enhances treatment efficacy. However, direct cytoplasmic drugs vaccines into cells has remained out reach. We find that liposomes studded with 0.8-nm-wide carbon nanotube porins (CNTPs) function as efficient vehicles for drug by facilitating fusion lipid membranes complete mixing the membrane material vesicle interior content. Fusion kinetics data coarse-grained molecular dynamics simulations...
The fusion of lipid membranes is opposed by high energetic barriers. In living organisms, complex protein machineries carry out this biologically essential process. Here we show that membrane-spanning carbon nanotubes (CNTs) can trigger spontaneous small vesicles. coarse-grained molecular dynamics simulations, find a CNT bridging between two vesicles locally perturbs their structure. Their outer leaflets merge as the pulls lipids membranes, creating an hourglass-shaped intermediate with...
We show that the rotational dynamics of proteins and nucleic acids determined from molecular simulations under periodic boundary conditions suffer significant finite-size effects. remove box-size dependence diffusion coefficients by adding a hydrodynamic correction kBT/6ηV with kB Boltzmann's constant, T absolute temperature, η solvent shear viscosity, V box volume. this accounts for horse-heart myoglobin B-DNA dodecamer in aqueous solution. The resulting radii are excellent agreement experiment.
Electric field fluctuations play a major role in dissociation reactions liquid water and determine its vibrational spectroscopic response. Here, we study the statistics of electric fields using molecular dynamics computer simulations with particular focus on strong but rare that drive dissociation. Our indicate important contributions to acting OH bonds stem from molecules less than 7 {\AA} away. Long-ranged minor role.
Abstract The demands on the accuracy of force fields for classical molecular dynamics simulations are steadily growing as larger and more complex systems studied over longer times. One way to meet these is hand learning their parameters machines in a systematic (semi)automatic manner. Doing so, we can take full advantage exascale computing, increasing availability experimental data, advances quantum mechanical computations calculation observables from ensembles. Here, discuss illustrate...
Double electron–electron resonance (DEER) experiments probe nanometer-scale distances in spin-labeled proteins and nucleic acids. Rotamer libraries of the covalently attached spin-labels help reduce position uncertainties. Here we show that rotamer reweighting is essential for precision distance measurements, making it possible to resolve Ångstrom-scale domain motions. We analyze extensive DEER measurements on three N-terminal polypeptide transport-associated (POTRA) domains outer membrane...
We present a method to calculate the fully anisotropic rotational diffusion tensor from molecular dynamics simulations. Our approach is based on fitting time-dependent covariance matrix of quaternions that describe rigid-body dynamics. Explicit analytical expressions have been derived for covariances by Favro, which are valid irrespective degree anisotropy. use these determine an optimal trajectory data. The structures aligned against reference superposition. quaternion can then be obtained...
Predicting the costructure of small-molecule ligands and their respective target proteins has been a long-standing problem in drug discovery. For weak binding compounds typically identified fragment-based screening (FBS) campaigns, determination correct site mode is usually done experimentally via X-ray crystallography. many targets pharmaceutical interest, however, establishing an system which allows for sufficient throughput to support discovery project not possible. In this case,...
Lipid membranes are integral building blocks of living cells and perform a multitude biological functions. Currently, molecular simulations cellular-scale membrane remodeling processes at atomic resolution extremely difficult, due to their size, complexity, the large times-scales on which these occur. Instead, elastic models used simulate shapes transitions between them infer properties Unfortunately, an efficiently parallelized open-source simulation code do so has been lacking. Here, we...
The proper balancing of information from experiment and theory is a long-standing problem in the analysis noisy incomplete data. Viewed as Pareto optimization problem, improved agreement with experimental data comes at expense growing inconsistencies theoretical reference model. Here, we propose how to set exchange rate priori properly balance this trade-off. We focus on gentle ensemble refinement, where difference between potential energy surfaces refined models small thermal scale. By...
We present numerical calculations, simulation results, and analytical considerations for the frequency-dependent dielectric constant of single-file water in narrow nanopores, described by a recently developed dipole lattice model. find Debye relaxation over all length scales with times that strongly depend on pore length. This behavior is analyzed terms dynamics orientational defects leading to simple quantitative expressions static susceptibility time limits short long pores. Based these...
Polyketide synthases (PKSs) are versatile C-C bond-forming enzymes that broadly distributed in bacteria and fungi. The polyketide compound family includes many clinically useful drugs such as the antibiotic erythromycin, antineoplastic epothilone, cholesterol-lowering lovastatin. Harnessing PKSs for custom synthesis remains an open challenge, largely because of lack knowledge about key structural properties. Particularly, domains-well characterized on their own-are poorly understood...