Structures Controlled by Entropy: The Flexibility of Strychnine as Example

To study the flexibility of strychnine, we performed molecular dynamics simulations with orientational tensorial constraints (MDOC). Tensorial constraints are derived from nuclear magnetic resonance (NMR) interaction tensors, for instance, from residual dipolar couplings (RDCs). Used as orientational constraints, they rotate the whole molecule and molecular parts with low rotational barriers. Since the NMR parameters are measured at ambient temperatures, orientational constraints generate conformers that populate the whole landscape of Gibbs free energy. In MDOC, structures are populated that are not only controlled by energy but by the entropy term TΔS of the Gibbs free energy. In the case of strychnine, it is shown that ring conformers are populated, which has not been discussed in former investigations. These conformer populations are not only in accordance with RDCs but fulfill nuclear Overhauser effect (NOE)-derived distance constraints and $^{3}J_{HH}$ couplings as well

All-atom molecular dynamics simulations using orientational constraints from anisotropic NMR samples

Orientational constraints obtained from solid state NMR experiments on anisotropic samples are used here in molecular dynamics (MD) simulations for determining the structure and dynamics of several different membrane-bound molecules. The new MD technique is based on the inclusion of orientation dependent pseudo-forces in the COSMOS-NMR force field. These forces drive molecular rotations and re-orientations in the simulation, such that the motional time-averages of the tensorial NMR properties approach the experimentally measured parameters. The orientational-constraint-driven MD simulations are universally applicable to all NMR interaction tensors, such as chemical shifts, dipolar couplings and quadrupolar interactions. The strategy does not depend on the initial choice of coordinates, and is in principle suitable for any flexible molecule. To test the method on three systems of increasing complexity, we used as constraints some deuterium quadrupolar couplings from the literature on pyrene, cholesterol and an antimicrobial peptide embedded in oriented lipid bilayers. The MD simulations were able to reproduce the NMR parameters within experimental error. The alignment of the three membrane-bound molecules and some aspects of their conformation were thus derived from the NMR data, in good agreement with previous analyses. Furthermore, the new approach yielded for the first time the distribution of segmental orientations with respect to the membrane and the order parameter tensors of all three systems

Fast Atomic Charge Calculation for Implementation into a Polarizable Force Field and Application to an Ion Channel Protein

Polarization of atoms plays a substantial role in molecular interactions. Class I and II force fields mostly calculate with fixed atomic charges which can cause inadequate descriptions for highly charged molecules, for example, ion channels or metalloproteins. Changes in charge distributions can be included into molecular mechanics calculations by various methods. Here, we present a very fast computational quantum mechanical method, the Bond Polarization Theory (BPT). Atomic charges are obtained via a charge calculation method that depend on the 3D structure of the system in a similar way as atomic charges of ab initio calculations. Different methods of population analysis and charge calculation methods and their dependence on the basis set were investigated. A refined parameterization yielded excellent correlation of R=0.9967. The method was implemented in the force field COSMOS-NMR and applied to the histidine-tryptophan-complex of the transmembrane domain of the M2 protein channel of influenza A virus. Our calculations show that moderate changes of side chain torsion angle χ1 and small variations of χ2 of Trp-41 are necessary to switch from the inactivated into the activated state; and a rough two-side jump model of His-37 is supported for proton gating in accordance with a flipping mechanism

A Structurally Flexible Halide Solid Electrolyte with High Ionic Conductivity and Air Processability

In this work, a structurally revivable, chloride-ion conducting solid electrolyte (SE), CsSn$_{0.9}$In$_{0.067}$Cl$_3$, with a high ionic conductivity of 3.45 × 10$^{−4}$ S cm$^{−1}$ at 25 °C is investigated. The impedance spectroscopy, density functional theory, solid-state $^{35}$Cl NMR, and electron paramagnetic resonance studies collectively reveal that the high Cl$^−$ ionic mobility originates in the flexibility of the structural building blocks, Sn/InCl$_6$ octahedra. The vacancy-dominated Cl$^−$ ion diffusion encompasses co-ordinated Sn/In(Cl) site displacements that depend on the exact stoichiometry, and are accompanied by changes in the local magnetic moments. Owing to these promising properties, the suitability of the CsSn$_{0.9}$In$_{0.067}$Cl$_3$, as an electrolyte is demonstrated by designing all-solid-state batteries, with different anodes and cathodes. The comparative investigation of interphases with Li, Li–In, Mg, and Ca anodes reveals different levels of reactivity and interphase formation. The CsSn$_{0.9}$In$_{0.067}$Cl$_3$ demonstrates an excellent humidity tolerance (up to 50% relative humidity) in ambient air, maintaining high structural integrity without compromises in ionic conductivity, which stands in contrast to commercial halide-based lithium conductors. The discovery of a halide perovskite conductor, with air processability and structure revival ability paves the way for the development of advanced air processable SEs, for next-generation batteries

Three dimensional structure elucidation with COSMOS-NMR force field

The dissertation presented here stands in direct relationship to the topic of structure determination with NMR (nuclear magnetic resonance) parameters. In this work, the first general method for direct 3D-structure refinement using NMR magnetic shielding is introduced. This method is applicable for both solutions and solid states. The structure of a pseudotripeptide zinc complex in solution could be predicted, using the method. Furthermore, the proton positions of D-mannitol in the solid state were determined using crystal simulations, and the structure of a silk model was refined

Structures Controlled by Entropy: The Flexibility of Strychnine as Example

To study the flexibility of strychnine, we performed molecular dynamics simulations with orientational tensorial constraints (MDOC). Tensorial constraints are derived from nuclear magnetic resonance (NMR) interaction tensors, for instance, from residual dipolar couplings (RDCs). Used as orientational constraints, they rotate the whole molecule and molecular parts with low rotational barriers. Since the NMR parameters are measured at ambient temperatures, orientational constraints generate conformers that populate the whole landscape of Gibbs free energy. In MDOC, structures are populated that are not only controlled by energy but by the entropy term TΔS of the Gibbs free energy. In the case of strychnine, it is shown that ring conformers are populated, which has not been discussed in former investigations. These conformer populations are not only in accordance with RDCs but fulfill nuclear Overhauser effect (NOE)-derived distance constraints and 3JHH couplings as well

1H line width dependence on MAS speed in solid state NMR – comparison of experiment and simulation

Recent developments in magic angle spinning (MAS) technology permit spinning frequencies of >= 100 kHz. We examine the effect of such fast MAS rates upon nuclear magnetic resonance proton line widths in the multi-spin system of b-Asp-Ala crystal. We perform powder pattern simulations employing Fokker-Plank approach with periodic boundary conditions and 1H-chemical shift tensors calculated using the bond polarization theory. The theoretical predictions mirror well the experimental results. Both approaches demonstrate that homogeneous broadening has a linear-quadratic dependency on the inverse of the MAS spinning frequency and that, at the faster end of the spinning frequencies, the residual spectral line broadening becomes dominated by chemical shift distributions and susceptibility effects even for crystalline systems