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

该提案是在2020年至2022年期间执行的DFG-GAČR联合项目的后续应用。该项目专注于应用于淀粉样纤维和膜蛋白等生物固体的MAS(魔角旋转)固态核磁共振实验，这些固体仍然受到低灵敏度的阻碍。利用最优控制方法，我们开展了保相相干传输实验。对于多维相关实验中的每个间接采样光谱维度，该策略将实验的灵敏度提高了1.41倍，并在多维固态核磁共振实验中实现了大幅增强。同时，脉冲形状对射频误校有很强的抵抗力，并且便于用户友好的实验实现。在新的项目中，我们将引入自适应近似方法来计算自旋动力学，以加速最优控制优化。除了纯粹的数值模拟，我们还将使用有效的哈密顿理论，并利用重复脉冲序列元素来补偿大的射频场不均匀。我们将考虑具体的硬件问题，如射频不均匀、不同通道上的不平衡以及MAS的不稳定性，以进一步改进现有的脉冲序列。我们将应用相位保持方法来产生涉及侧链分配的CB化学位移的脉冲方案。我们将实施有效的甲基共振分配方法，并将在非常快的MAS上介绍用于结构确定的距离定量测量技术。该项目的潜在影响是巨大的，因为它将极大地促进利用MAS固态核磁共振对生物分子结构的常规表征所需的高维实验的实施和分析。

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.