Development of Optimal Control derived experiments for biological MAS solid-state NMR

点击翻译按钮获取中文摘要

This proposal is a follow-up application of a joint DFG-GAČR project carried out in the time period 2020-2022. The project focuses on MAS (Magic Angle Spinning) solid-state NMR experiments applied to biological solids like amyloid fibrils and membrane proteins that are still hampered by low sensitivity. Using optimal control methods, we developed phase-preserving coherence transfer experiments. This strategy improves the sensitivity of the experiment by a factor of >1.41 for each indirectly sampled spectral dimension in multidimensional correlation experiments and enables large enhancements in multidimensional solid-state NMR experiments. At the same time, pulse shapes are robust against rf miscalibration and facilitate a user-friendly experimental implementation. In the new project, we will introduce adaptive approximation methods for spin dynamics calculations to accelerate optimal control optimizations. In addition to purely numerical simulations, we will employ effective Hamiltonian theory and make use of repetitive pulse sequence elements to compensate for large RF field inhomogeneities. We will consider specific hardware issues such as rf inhomogeneity imbalances on different channels as well as MAS instabilities to improve existing pulse sequences further. We will apply phase-preserving methodologies to yield pulse schemes that involve CB chemical shifts for side chain assignments. We will implement efficient methods for assigning methyl resonances, and we will introduce techniques for the quantitative measurement of distances for structure determination at very fast MAS. The potential impact of the project is enormous, as it will greatly facilitate the implementation and analysis of higher dimensional experiments required for the routine characterization of biomolecular structures by MAS solid-state NMR.