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MultiSig: a new high-precision approach to the analysis of complex biomolecular systems

机译:MultiSig:一种用于复杂生物分子系统分析的高精度新方法

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摘要

MultiSig is a newly developed mode of analysis of sedimentation equilibrium (SE) experiments in the analytical ultracentrifuge, having the capability of taking advantage of the remarkable precision (~0.1 % of signal) of the principal optical (fringe) system employed, thus supplanting existing methods of analysis through reducing the ‘noise’ level of certain important parameter estimates by up to orders of magnitude. Long-known limitations of the SE method, arising from lack of knowledge of the true fringe number in fringe optics and from the use of unstable numerical algorithms such as numerical differentiation, have been transcended. An approach to data analysis, akin to ‘spatial filtering’, has been developed, and shown by both simulation and practical application to be a powerful aid to the precision with which near-monodisperse systems can be analysed, potentially yielding information on protein-solvent interaction. For oligo- and poly-disperse systems the information returned includes precise average mass distributions over both cell radial and concentration ranges and mass-frequency histograms at fixed radial positions. The application of MultiSig analysis to various complex heterogenous systems and potentially multiply-interacting carbohydrate oligomers is described.
机译:MultiSig是分析超速离心机中沉降平衡(SE)实验分析的一种新开发模式,具有利用所采用的主要光学(条纹)系统卓越的精度(〜信号的0.1%)的能力,从而取代了现有技术通过将某些重要参数估计的“噪声”水平降低多达几个数量级的分析方法。由于缺乏对条纹光学中真实条纹数的了解以及使用不稳定的数值算法(例如数值微分)而导致的SE方法的长期局限性已被超越。已经开发了一种类似于“空间过滤”的数据分析方法,并且通过仿真和实际应用表明,该方法可以大大提高分析近单分散系统的精度,从而可能产生有关蛋白质溶剂的信息相互作用。对于低分散和多分散系统,返回的信息包括在细胞径向和浓度范围内的精确平均质量分布以及在固定径向位置的质频直方图。描述了将MultiSig分析应用于各种复杂的异质系统和潜在的多重相互作用的碳水化合物低聚物。

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