Maximum Entropy Deconvolution for Resolution & Sensitivity Enhancement in Bio-NMR

描述（由申请人提供）：核磁共振（NMR）光谱是探测生物分子结构、动力学和相互作用的最通用工具之一。它是唯一能够以原子分辨率确定溶液中分子结构的方法，并且具有许多重要的生物医学应用，包括筛选潜在的候选药物和定量生物流体或完整细胞中的代谢物。灵敏度和 分辨率在生物分子NMR中提出了双重挑战。通过在可达到的最高磁场下进行实验，在昂贵得惊人的仪器上进行实验，两者都得到了改善。信号处理方法也长期用于NMR中，以最大限度地提高灵敏度和分辨率。基于傅立叶变换的信号处理的线性方法总是遇到灵敏度/分辨率的权衡，其中一个可以以另一个为代价来增强，但两者不能同时优化。非线性频谱分析方法在某些情况下可以避免这种折衷，同时提高灵敏度和分辨率。已经报道了使用最大熵反卷积在一维中同时提高灵敏度和分辨率的轶事示例，但是用这种方法实现的增益通常是适度的。在这个项目中，我们将开发使用最大熵同时去卷积两个或更多个维度以提高灵敏度和分辨率的方法。初步数据表明，与一维反卷积相比，灵敏度和分辨率的所得增益大幅增加，并且与在高得多的磁场下收集数据相关的增益相当。

DESCRIPTION (provided by applicant): Nuclear magnetic resonance (NMR) spectroscopy is one of the most versatile tools available for probing biomolecular structure, dynamics, and interactions. It is the only method capable of determining molecular structure in solution at atomic resolution, and it has a host of important biomedical applications, including screening potential drug candidates and quantifying metabolites in biofluids or intact cells. Sensitivity and resolution present twin challenges in biomolecular NMR. Both are improved by performing experiments at the highest attainable magnetic field, on instruments that can be staggeringly expensive. Signal processing methods have also long been used in NMR to enhance sensitivity and resolution to the fullest possible extent. Linear methods of signal processing based on the Fourier transform invariably encounter a sensitivity/resolution tradeoff, where one can be enhanced at the expense of the other, but both cannot be simultaneously optimized. Nonlinear methods of spectrum analysis can in some cases avoid this tradeoff, and simultaneously improve both sensitivity and resolution. Anecdotal examples of simultaneously improving sensitivity and resolution in one dimension using maximum entropy deconvolution have been reported, but the gains achieved with this approach are typically modest. In this project we will develop methods for employing maximum entropy to simultaneously deconvolve two or more dimensions to enhance sensitivity and resolution. Preliminary data indicate the resulting gains in sensitivity and resolution are substantially increased compared to one-dimensional deconvolution, and are comparable to the gains associated with collecting data at much higher magnetic field.