Proton detection in solid state NMR is continuously developing and allows one to gain new insights in structural biology. Overall, this progress is a result of the synergy between hardware development, new NMR methodology and new isotope labeling strategies, to name a few factors. Even though current developments are rapid, it is worthwhile to summarize what can currently be achieved employing proton detection in biological solids. We illustrate this by analysing the signal-to-noise ratio (SNR) for spectra obtained for a microcrystalline α-spectrin SH3 domain protein sample by (i) employing different degrees of chemical dilution to replace protons by incorporating deuterons in different sites, by (ii) variation of the magic angle spinning (MAS) frequencies between 20 and 110 kHz, and by (iii) variation of the static magnetic field B₀. The experimental SNR values are validated with numerical simulations employing up to 9 proton spins. Although in reality a protein would contain far more than 9 protons, in a deuterated environment this is a sufficient number to achieve satisfactory simulations consistent with the experimental data. The key results of this analysis are (i) with current hardware, deuteration is still necessary to record spectra of optimum quality; (ii) 13CH3 isotopomers for methyl groups yield the best SNR when MAS frequencies above 100 kHz are available; and (iii) sensitivity increases with a factor beyond B0 3/2 with the static magnetic field due to a transition of proton-proton dipolar interactions from a strong to a weak coupling limit.

固态 NMR 中的质子检测不断发展，使人们能够获得结构生物学的新见解。总的来说，这一进展是硬件开发、新 NMR 方法和新同位素标记策略等因素协同作用的结果。尽管目前的发展很快，但值得总结一下目前在生物固体中使用质子检测可以实现的目标。我们通过分析微晶 α-血影蛋白 SH3 结构域蛋白样品的光谱的信噪比 (SNR) 来说明这一点，方法是 (i) 使用不同程度的化学稀释通过在不同位点掺入氘核来替换质子，通过 ( ii) 魔角自旋 (MAS) 频率在 20 和 110 kHz 之间的变化，以及 (iii) 静磁场 B 的变化₀。实验 SNR 值通过采用多达 9 个质子自旋的数值模拟进行验证。虽然实际上蛋白质包含的质子数量远远超过 9 个，但在氘化环境中，这个数量足以实现与实验数据一致的令人满意的模拟。该分析的主要结果是 (i) 使用当前的硬件，仍然需要氘化以记录最佳质量的光谱；(ii) 当 MAS 频率高于 100 kHz 时，甲基的 13CH3 同位素异构体产生最佳 SNR；(iii) 由于质子-质子偶极相互作用从强耦合极限到弱耦合极限的转变，灵敏度随静态磁场的因子超过 B0 3/2 而增加。