The Experts below are selected from a list of 261 Experts worldwide ranked by ideXlab platform
Goran Widmalm - One of the best experts on this subject based on the ideXlab platform.
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glycan flexibility insights into nanosecond dynamics from a microsecond molecular dynamics simulation explaining an unusual nuclear Overhauser Effect
Carbohydrate Research, 2010Co-Authors: Jens Landstrom, Goran WidmalmAbstract:An atomistic all-atom molecular dynamics simulation of the trisaccharide beta-D-ManpNAc-(1-->4)[alpha-D-Glcp-(1-->3)]-alpha-L-Rhap-OMe with explicit solvent molecules has been carried out. The trisaccharide represents a model for the branching region of the O-chain polysaccharide of a strain from Aeromonas salmonicida. The extensive MD simulations having a 1-micros duration revealed a conformational dynamics process on the nanosecond time scale, that is, a 'time window' not extensively investigated for carbohydrates to date. The results obtained from the MD simulation underscore the predictive power of molecular simulations in studies of biomolecular systems and also explain an unusual nuclear Overhauser Effect originating from conformational exchange.
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a conformational study of the vicinally branched trisaccharide d glcp 1 2 d glcp 1 3 d manp ome by nuclear Overhauser Effect spectroscopy noesy and transverse rotating frame Overhauser Effect spectroscopy troesy experiments comparison to monte carlo
Biopolymers, 1999Co-Authors: Alexandra Kjellberg, Goran WidmalmAbstract:The trisaccharide beta-D-Glcp-(1 --> 2)[beta-D-Glcp-(1 --> 3)]alpha-D-Manp-OMe, a model for branching regions in oligosaccharides, has been investigated by one-dimensional DPFGSE (1)H, (1)H nuclear Overhauser Effect spectroscopy (NOESY) and transverse rotating-frame Overhauser Effect spectroscopy (TROESY) experiments at 30 degrees C in water and in the solvent mixture water : dimethyl sulfoxide (7 : 3). Cross-relaxation rates were obtained from the nmr experiments and interpreted as proton-proton distances. From Metropolis Monte Carlo and Langevin dynamics simulations, distances were calculated and compared to those obtained from experiment. Using the previously determined dynamics from carbon-13 nmr relaxation measurements of the trisaccharide in the solvent mixture, intraresidue proton distances could be obtained that were in excellent to reasonable agreement with those calculated from simulations. In water, the isolated spin-pair approximation was used for comparison of interproton distances. The experimentally derived distances in both solvents showed that the trans-glycosidic distances were shorter between the anomeric proton of the glucosyl group and the proton at the linkage position, respectively, than to the proton on the adjacent carbon on the mannosyl residue. The interresidue distances calculated from the computer simulations, performed with three different force fields, namely HSEA, PARM22, and CHEAT95, resulted in the reverse order in all cases but one.
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a conformational study of the vicinally branched trisaccharide beta d glcp 1 2 beta d glcp 1 3 alpha d manp ome by nuclear Overhauser Effect spectroscopy noesy and transverse rotating frame Overhauser Effect spectroscopy troesy experiments comparison
Biopolymers, 1999Co-Authors: Alexandra Kjellberg, Goran WidmalmAbstract:The trisaccharide beta-D-Glcp-(1 --> 2)[beta-D-Glcp-(1 --> 3)]alpha-D-Manp-OMe, a model for branching regions in oligosaccharides, has been investigated by one-dimensional DPFGSE (1)H, (1)H nuclear Overhauser Effect spectroscopy (NOESY) and transverse rotating-frame Overhauser Effect spectroscopy (TROESY) experiments at 30 degrees C in water and in the solvent mixture water : dimethyl sulfoxide (7 : 3). Cross-relaxation rates were obtained from the nmr experiments and interpreted as proton-proton distances. From Metropolis Monte Carlo and Langevin dynamics simulations, distances were calculated and compared to those obtained from experiment. Using the previously determined dynamics from carbon-13 nmr relaxation measurements of the trisaccharide in the solvent mixture, intraresidue proton distances could be obtained that were in excellent to reasonable agreement with those calculated from simulations. In water, the isolated spin-pair approximation was used for comparison of interproton distances. The experimentally derived distances in both solvents showed that the trans-glycosidic distances were shorter between the anomeric proton of the glucosyl group and the proton at the linkage position, respectively, than to the proton on the adjacent carbon on the mannosyl residue. The interresidue distances calculated from the computer simulations, performed with three different force fields, namely HSEA, PARM22, and CHEAT95, resulted in the reverse order in all cases but one.
Othmar Steinhauser - One of the best experts on this subject based on the ideXlab platform.
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the nuclear Overhauser Effect noe as a tool to study macromolecular confinement elucidation and disentangling of crowding and encapsulation Effects
Journal of Chemical Physics, 2020Co-Authors: Philipp Honegger, Othmar SteinhauserAbstract:We propose a methodology to capture short-lived but biophysically important contacts of biomacromolecules using the biomolecule-water nuclear Overhauser Effect as an indirect microscope. Thus, instead of probing the direct correlation with the foreign biomolecule, we detect its presence by the disturbance it causes in the surrounding water. In addition, this information obtained is spatially resolved and can thus be attributed to specific sites. We extend this approach to the influence of more than one change in chemical environment and show a methodological way of resolution. This is achieved by taking double differences of corresponding σNOE/σROE ratios of the systems studied and separating specific, unspecific, and intermediate influence. While applied to crowding and encapsulation in this study, this method is generally suitable for any combination of changes in chemical environment.
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the protein water nuclear Overhauser Effect noe as an indirect microscope for molecular surface mapping of interaction patterns
Physical Chemistry Chemical Physics, 2020Co-Authors: Philipp Honegger, Othmar SteinhauserAbstract:In this computational study, the intermolecular solute-solvent Nuclear Overhauser Effect (NOE) of the model protein ubiquitin in different chemical environments (free, bound to a partner protein and encapsulated) is investigated. Short-ranged NOE observables such as the NOE/ROE ratio reveal hydration phenomena on absolute timescales such as fast hydration sites and slow water clefts. We demonstrate the ability of solute-solvent NOE differences measured of the same protein in different chemical environments to reveal hydration changes on the relative timescale. The resulting NOE/ROE-surface maps are shown to be a central key for analyzing biologically relevant chemical influences such as complexation and confinement: the presence of a complexing macromolecule or a confining surface wall modulates the water mobility in the vicinity of the probe protein, hence revealing which residues of said protein are proximate to the foreign interface and which are chemically unaffected. This way, hydration phenomena can serve to indirectly map the precise influence (position) of other molecules or interfaces onto the protein surface. This proposed one-protein many-solvents approach may offer experimental benefits over classical one-protein other-protein pseudo-intermolecular transient NOEs. Furthermore, combined influences such as complexation and confinement may exert non-additive influences on the protein compared to a reference state. We offer a mathematical method to disentangle the influence of these two different chemical environments.
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changes in protein hydration dynamics by encapsulation or crowding of ubiquitin strong correlation between time dependent stokes shift and intermolecular nuclear Overhauser Effect
RSC Advances, 2019Co-Authors: Philipp Honegger, Christian Schroder, Esther Heid, Stella Schmode, Othmar SteinhauserAbstract:The local changes in protein hydration dynamics upon encapsulation of the protein or macromolecular crowding are essential to understand protein function in cellular environments. We were able to obtain a spatially-resolved picture of the influence of confinement and crowding on the hydration dynamics of the protein ubiquitin by analyzing the time-dependent Stokes shift (TDSS), as well as the intermolecular Nuclear Overhauser Effect (NOE) at different sites of the protein by large-scale computer simulation of single and multiple proteins in water and confined in reverse micelles. Besides high advanced space resolved information on hydration dynamics we found a strong correlation of the change in NOE upon crowding or encapsulation and the change in the integral TDSS relaxation times in all investigated systems relative to the signals in a diluted protein solution.
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revival of the intermolecular nuclear Overhauser Effect for mapping local protein hydration dynamics
Journal of Physical Chemistry Letters, 2017Co-Authors: Daniel Braun, Michael Schmollngruber, Othmar SteinhauserAbstract:The highly heterogeneous hydration dynamics of protein–water interfaces is considered important for protein stability and dynamics, protein folding, enzymatic activity, and even drug design. The nuclear Overhauser Effect (NOE) between protein and water protons is the only experimental observable which, in principle, can provide a map of locally resolved hydration dynamics. However, its utility was questioned in various theoretical studies that emphasized the contributions of long-range NOE interactions. We show by a detailed analysis based on molecular dynamics simulations that, contrary to recent claims, the protein–water NOE is an excellent observable to map local hydration dynamics at the protein surface.
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pair dynamics and the intermolecular nuclear Overhauser Effect noe in liquids analysed by simulation and model theories application to an ionic liquid
Journal of Chemical Physics, 2014Co-Authors: Sonja Gabl, Daniel Braun, Christian Schroder, Hermann Weingartner, Othmar SteinhauserAbstract:Combining simulation and model theories, this paper analyses the impact of pair dynamics on the intermolecular nuclear Overhauser Effect (NOE) in liquids. For the first time, we give a distance resolved NOE. When applied to the ionic liquid 1-ethyl-3-methyl-imidazolium tetrafluoroborate the NOE turns out to be of long-range nature. This behaviour translates to the experimentally measured cross- and longitudinal relaxation rates. We were able to calculate the heteronuclear NOE from simulation data, despite the high computational effort. Model theories are computationally less demanding and cover the complete frequency range of the respective spectral density function, they are usually based on a very simple pair distribution function and the solution of the diffusion equation. In order to model the simulated data sufficiently, these simplifications in structure and dynamics have to be generalised considerably.
Alexandra Kjellberg - One of the best experts on this subject based on the ideXlab platform.
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a conformational study of the vicinally branched trisaccharide d glcp 1 2 d glcp 1 3 d manp ome by nuclear Overhauser Effect spectroscopy noesy and transverse rotating frame Overhauser Effect spectroscopy troesy experiments comparison to monte carlo
Biopolymers, 1999Co-Authors: Alexandra Kjellberg, Goran WidmalmAbstract:The trisaccharide beta-D-Glcp-(1 --> 2)[beta-D-Glcp-(1 --> 3)]alpha-D-Manp-OMe, a model for branching regions in oligosaccharides, has been investigated by one-dimensional DPFGSE (1)H, (1)H nuclear Overhauser Effect spectroscopy (NOESY) and transverse rotating-frame Overhauser Effect spectroscopy (TROESY) experiments at 30 degrees C in water and in the solvent mixture water : dimethyl sulfoxide (7 : 3). Cross-relaxation rates were obtained from the nmr experiments and interpreted as proton-proton distances. From Metropolis Monte Carlo and Langevin dynamics simulations, distances were calculated and compared to those obtained from experiment. Using the previously determined dynamics from carbon-13 nmr relaxation measurements of the trisaccharide in the solvent mixture, intraresidue proton distances could be obtained that were in excellent to reasonable agreement with those calculated from simulations. In water, the isolated spin-pair approximation was used for comparison of interproton distances. The experimentally derived distances in both solvents showed that the trans-glycosidic distances were shorter between the anomeric proton of the glucosyl group and the proton at the linkage position, respectively, than to the proton on the adjacent carbon on the mannosyl residue. The interresidue distances calculated from the computer simulations, performed with three different force fields, namely HSEA, PARM22, and CHEAT95, resulted in the reverse order in all cases but one.
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a conformational study of the vicinally branched trisaccharide beta d glcp 1 2 beta d glcp 1 3 alpha d manp ome by nuclear Overhauser Effect spectroscopy noesy and transverse rotating frame Overhauser Effect spectroscopy troesy experiments comparison
Biopolymers, 1999Co-Authors: Alexandra Kjellberg, Goran WidmalmAbstract:The trisaccharide beta-D-Glcp-(1 --> 2)[beta-D-Glcp-(1 --> 3)]alpha-D-Manp-OMe, a model for branching regions in oligosaccharides, has been investigated by one-dimensional DPFGSE (1)H, (1)H nuclear Overhauser Effect spectroscopy (NOESY) and transverse rotating-frame Overhauser Effect spectroscopy (TROESY) experiments at 30 degrees C in water and in the solvent mixture water : dimethyl sulfoxide (7 : 3). Cross-relaxation rates were obtained from the nmr experiments and interpreted as proton-proton distances. From Metropolis Monte Carlo and Langevin dynamics simulations, distances were calculated and compared to those obtained from experiment. Using the previously determined dynamics from carbon-13 nmr relaxation measurements of the trisaccharide in the solvent mixture, intraresidue proton distances could be obtained that were in excellent to reasonable agreement with those calculated from simulations. In water, the isolated spin-pair approximation was used for comparison of interproton distances. The experimentally derived distances in both solvents showed that the trans-glycosidic distances were shorter between the anomeric proton of the glucosyl group and the proton at the linkage position, respectively, than to the proton on the adjacent carbon on the mannosyl residue. The interresidue distances calculated from the computer simulations, performed with three different force fields, namely HSEA, PARM22, and CHEAT95, resulted in the reverse order in all cases but one.
Brian D Sykes - One of the best experts on this subject based on the ideXlab platform.
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interaction of troponin i and troponin c use of the two dimensional nuclear magnetic resonance transferred nuclear Overhauser Effect to determine the structure of the inhibitory troponin i peptide when bound to skeletal troponin c
Journal of Molecular Biology, 1991Co-Authors: A P Campbell, Brian D SykesAbstract:Abstract We have used two-dimensional 1 H nuclear magnetic resonance spectroscopy to determine the structure of the synthetic inhibitory peptide N α-acetyl TnI(104–115) amide bound to calcium-saturated skeletal troponin C (TnC). Conformational changes in the peptide induced by the formation of the troponin I (TnI) peptide-TnC complex were followed by the study of the transferred nuclear Overhauser Effect, a technique that allows one to determine the structure of a ligand bound to a macromolecule. The structure of the bound TnI peptide reveals an amphiphilic α-helix, distorted around the two central proline residues. The central bend in the peptide functions to bring the residues on the hydrophobic face into closer proximity with each other, thereby forming a small hydrophobic pocket. The hydrophilic, basic residues extend off the opposite face of the peptide. Hydrophobic surfaces on TnC that become exposed upon binding of calcium are involved in the binding of the TnI peptide, but electrostatic interactions also contribute to the strength of the interaction. The role of amphiphilic helices in the targeting of calcium-binding proteins such as troponin C will be discussed.
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theoretical evaluation of the two dimensional transferred nuclear Overhauser Effect
Journal of Magnetic Resonance, 1991Co-Authors: Patricia A Campbell, Brian D SykesAbstract:Abstract A theoretical evaluation of the two-dimensional intramolecular transferred nuclear Overhauser Effect (TRNOE) is presented using a full relaxation matrix approach. The application of this analysis to the study of 6-24 residue peptides binding to proteins ranging in size from 18,000 to 80,000 Da is considered. The Effects of variables such as mixing time, fraction of bound peptide, free and bound correlation times, and other contributions to spin-lattice relaxation rates are examined in an attempt to offer practical experimental guidelines for the design of a TRNOE experiment.
Harald E Moller - One of the best experts on this subject based on the ideXlab platform.
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a new approach to z spectrum acquisition prospective baseline enhancement probe for cest nuclear Overhauser Effect
Magnetic Resonance in Medicine, 2019Co-Authors: Tobias Lenich, Andre Pampel, Toralf Mildner, Harald E MollerAbstract:Purpose To develop a prospective baseline enhancement that compensates for intermingled background Effects in Z-spectra to achieve sensitivity enhancement of peaks related to CEST and nuclear Overhauser Effect. Methods An MRI sequence-specific compensation of background Effects is achieved through variation of the pulsed saturation power, ω 1 , max , with the chemical shift, δ . After a "scout acquisition" of a standard Z-spectrum, the background is modeled through an appropriate spin system. Subsequently, an optimization procedure yields ω 1 , m a x ( δ ) values that compensate for background contributions yielding a flat baseline. Contributions from metabolites not considered in the optimization procedure are enhanced as distinct perturbations to the baseline. For experimental verification, mapping of the lactate concentration in the presence of cross-linked bovine serum albumin was performed in phantoms at 7 T. As proof of concept, explorative experiments were performed in healthy human subjects at 3 T. Results Nuisance contributions from direct water saturation, macromolecular magnetization transfer, and exchanging background protons were successfully removed from the Z-spectrum in phantoms and in brain tissue. The lactate methyl, methine, and hydroxyl peaks were readily observable in vitro. The peak areas correlated linearly with known concentrations. Improvement of the detection limit was achieved by a sparse distribution of saturation frequencies, allowing for more efficient signal averaging. Conclusion An optimization framework for high-resolution metabolite mapping by means of CEST/nuclear Overhauser Effect was developed. It offers full flexibility to select spin-pool moieties, whose influence on the Z-spectrum will be compensated. Deviations from this background model will provide a contrast at the respective offset frequencies.
