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

该提案是2020-2022年期间开展的DFG-GAČR联合项目的后续应用。该项目的重点是MAS（魔角旋转）固态NMR实验应用于生物固体，如淀粉样纤维和膜蛋白，仍然受到低灵敏度的阻碍。利用最优控制方法，我们开发了相位保持相干传输实验。这种策略在多维相关实验中对于每个间接采样的光谱维度将实验的灵敏度提高了>1.41倍，并且能够大幅增强多维固态NMR实验。同时，脉冲形状对射频误校准是鲁棒的，并有利于用户友好的实验实施。在这个新项目中，我们将引入自适应近似方法用于自旋动力学计算，以加速最优控制优化。除了纯粹的数值模拟，我们将采用有效的哈密顿理论，并利用重复的脉冲序列元素，以补偿大的RF场的不均匀性。我们将考虑具体的硬件问题，如射频不均匀性不平衡，不同的渠道，以及MAS的不稳定性，以进一步改善现有的脉冲序列。我们将应用保相方法产生脉冲方案，涉及CB化学位移的侧链分配。我们将实施有效的方法分配甲基共振，我们将介绍技术的定量测量的距离，在非常快的MAS结构测定。该项目的潜在影响是巨大的，因为它将极大地促进MAS固态NMR生物分子结构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.