| 1. |
- Pendrill, Robert, 1984-, et al.
(författare)
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Flexibility at a glycosidic linkage revealed by molecular dynamics, stochastic modeling, and 13C NMR spin relaxation : conformational preferences of alpha-L-Rhap-alpha-(1 -> 2)-alpha-L-Rhap-OMe in water and dimethyl sulfoxide solutions
- 2016
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 18:4, s. 3086-3096
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Tidskriftsartikel (refereegranskat)abstract
- The monosaccharide L-rhamnose is common in bacterial polysaccharides and the disaccharide alpha-L-Rhap-alpha-(1 -> 2)-alpha-L-Rhap-OMe represents a structural model for a part of Shigella flexneri O-antigen polysaccharides. Utilization of [1'-C-13]-site-specific labeling in the anomeric position at the glycosidic linkage between the two sugar residues facilitated the determination of transglycosidic NMR (3)J(CH) and (3)J(CC) coupling constants. Based on these spin-spin couplings the major state and the conformational distribution could be determined with respect to the psi torsion angle, which changed between water and dimethyl sulfoxide (DMSO) as solvents, a finding mirrored by molecular dynamics (MD) simulations with explicit solvent molecules. The C-13 NMR spin relaxation parameters T-1, T-2, and heteronuclear NOE of the probe were measured for the disaccharide in DMSO-d(6) at two magnetic field strengths, with standard deviations <= 1%. The combination of MD simulation and a stochastic description based on the diffusive chain model resulted in excellent agreement between calculated and experimentally observed C-13 relaxation parameters, with an average error of <2%. The coupling between the global reorientation of the molecule and the local motion of the spin probe is deemed essential if reproduction of NMR relaxation parameters should succeed, since decoupling of the two modes of motion results in significantly worse agreement. Calculation of C-13 relaxation parameters based on the correlation functions obtained directly from the MD simulation of the solute molecule in DMSO as solvent showed satisfactory agreement with errors on the order of 10% or less.
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| 2. |
- Zerbetto, Mirco, et al.
(författare)
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An integrated approach to NMR spin relaxation in flexible biomolecules: Application to β-D-glucopyranosyl-(1→6)-α-D-mannopyranosyl-OMe
- 2009
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Ingår i: Journal of Chemical Physics. - : American Institute of Physics. - 0021-9606 .- 1089-7690. ; 131:23, s. p234501-
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Tidskriftsartikel (refereegranskat)abstract
- The description of the reorientational dynamics of flexible molecules is a challenging task, in particular when the rates of internal and global motions are comparable. The commonly used simple mode-decoupling models are based on the assumption of statistical independence between these motions. This assumption is not valid when the time scale separation between their rates is small, a situation that was found to arise in oligosaccharides in the context of certain internal motions. To make possible the interpretation of NMR spin relaxation data from such molecules, we developed a comprehensive approach generally applicable to flexible rotators with one internal degree of freedom. This approach integrates a stochastic description of coupled global tumbling and internal torsional motion, quantum chemical calculations of the local potential and the local geometry at the site of the restricted torsion, and hydrodynamics-based calculations of the diffusive properties. The method is applied to the disaccharide -D-Glcp-(16)--D-[6-13C]-Manp-OMe dissolved in a DMSO-d6/D2O cryosolvent. The experimental NMR relaxation parameters, associated with the 13CH2 probe residing at the glycosidic linkage, include 13C T1 and T2 and 13C-{1H} nuclear Overhauser enhancement (NOE) as well as longitudinal and transverse dipole-dipole cross-correlated relaxation rates, acquired in the temperature range of 253–293 K. These data are predicted successfully by the new theory with only the H–C–H angle allowed to vary. Previous attempts to fit these data using mode-decoupling models failed.
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| 3. |
- Zerbetto, Mirco, et al.
(författare)
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Differential Dynamics at Glycosidic Linkages of an Oligosaccharide as Revealed by C-13 NMR Spin Relaxation and Stochastic Modeling
- 2018
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 122:8, s. 2287-2294
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Tidskriftsartikel (refereegranskat)abstract
- Among biomolecules, carbohydrates are unique in that not only can linkages be formed through different positions, but the structures may also be branched. The trisaccharide beta-D-Glcp-(1 -> 3)[beta-D-Glcp-(1 -> 2)]-alpha-D-Manp-OMe represents a model of a branched vicinally disubstituted structure. A C-13 site -specific isotopologue, with labeling in each of the two terminal glucosyl residues, enabled the acquisition of high-quality C-13 NMR relaxation parameters, T-1 and T-2, and heteronuclear NOE, with standard deviations of <= 0.5%. For interpretation of the experimental NMR data, a diffusive chain model was used, in which the dynamics of the glycosidic linkages is coupled to the global reorientation motion of the trisaccharide. Brownian dynamics simulations relying on the potential of mean force at the glycosidic linkages were employed to evaluate spectral densities of the spin probes. Calculated NMR relaxation parameters showed a very good agreement with experimental data, deviating <3%. The resulting dynamics are described by correlation times of 196 and 174 ps for the beta-(1 -> 2)- and beta-(1 -> 3)-linked glucosyl residues, respectively, i.e., different and linkage dependent. Notably, the devised computational protocol was performed without any fitting of parameters.
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| 4. |
- Zerbetto, Mirco, et al.
(författare)
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Glycosidic linkage flexibility : The psi torsion angle has a bimodal distribution in alpha-L-Rhap-(1 -> 2)-alpha-L-Rhap-OMe as deduced from C-13 NMR spin relaxation
- 2020
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 152:3
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Tidskriftsartikel (refereegranskat)abstract
- The molecular dynamics (MD) computer simulation technique is powerful for the investigation of conformational equilibrium properties of biomolecules. In particular, free energy surfaces of the torsion angles (those degrees of freedom from which the geometry mostly depends) allow one to access conformational states, as well as kinetic information, i.e., if the transitions between conformational states occur by simple jumps between wells or if conformational regions close to these states also are populated. The information obtained from MD simulations may depend substantially on the force field employed, and thus, a validation procedure is essential. NMR relaxation data are expected to be highly sensitive to the details of the torsional free energy surface. As a case-study, we consider the disaccharide alpha-l-Rhap-(1 -> 2)-alpha-l-Rhap-OMe that features only two important torsion angles, phi and psi, which define the interglycosidic orientation of the sugar residues relative to each other, governed mainly by the exo-anomeric effect and steric interactions, respectively. In water, a psi(-) state is preferred, whereas in DMSO, it is a psi(+) state, suggesting inherent flexibility at the torsion angle. MD simulations indicated that bistable potentials describe the conformational region well. To test whether a unimodal distribution suffices or if a bimodal distribution better represents molecular conformational preferences, we performed an alchemical morphing of the torsional free energy surface and computed T-1, T-2, and NOE C-13 NMR relaxation data that were compared to experimental data. All three NMR observables are substantially affected by the morphing procedure, and the results strongly support a bimodal Boltzmann equilibrium density with a major and a minor conformational state bisected at psi approximate to 0 degrees, in accord with MD simulations in an explicit solvent.
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| 5. |
- Zerbetto, Mirco, et al.
(författare)
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Stochastic Modeling of Flexible Biomolecules Applied to NMR Relaxation : I. Internal Dynamics of Cyclodextrins; y-Cyclodextrin as a Case Study
- 2012
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 116:44, s. 13159-13171
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we address the description of the dynamics of cyclodextrins in relation with nuclear magnetic resonance (NMR) relaxation data collected for hydroxymethyl groups. We define an integrated computational approach based on the definition and parametrization of a stochastic equation able to describe the relevant degrees of freedom affecting the NMR observables. The computational protocol merges molecular dynamics simulations and hydrodynamics approaches for the evaluation of most of the molecular parameters entering the stochastic description of the system. We apply the method to the interpretation of the C-13 NMR relaxation of the -CH2OH group of cyclodextrins. We use gamma-cyclodextrin as a case study. Results are in agreement with quantitative and qualitative analyses performed in the past with simpler models and molecular dynamics simulations. The element of novelty in our approach is in the treatment of the coupling of the relevant internal (glucopyranose ring twisting/tilting and hydroxymethyl group jumps) and global (molecular tumbling) degrees of freedom.
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