Parsimonious Charge Deconvolution for Native Mass Spectrometry.
Parsimonious Charge Deconvolution for Native Mass Spectrometry.
复制标题
DOI：
10.1021/acs.jproteome.7b00839
复制
发表时间：
2018-03-02
影响因子：
4.4
通讯作者：
Heck AJR
中科院分区：
文献类型：
--
作者：
Bern M;Caval T;Kil YJ;Tang W;Becker C;Carlson E;Kletter D;Sen KI;Galy N;Hagemans D;Franc V;Heck AJR
电荷去卷积从电喷雾电离质谱图中的质量过电荷(m/z)测量中推断出质量。当应用于宽输入m/z或宽目标质量范围时，电荷去卷积算法可能产生伪影，例如在正确质量的一半或三分之一处产生假质量。事实上，最常用的电荷去卷积算法MaxEnt的目标函数中的最大熵项有利于具有多个峰的去卷积谱而不是具有较少峰的去卷积谱。在这里，我们描述了一个新的“节俭”电荷反卷积算法，它产生的伪影更少。该算法特别适用于完整糖蛋白和蛋白质复合体的高分辨率天然质谱学。由于盐和小分子加合物、多聚体、宽质量范围以及更少和更低的电荷态，自然质量谱的去卷积带来了特殊的挑战。我们在一系列样本上演示了新的去卷积算法的性能。对于高度糖基化的血浆备解素糖蛋白，新算法可以同时去卷积单体和二聚体，当聚焦于单体的m/z范围时，对于以前使用m/z峰而不是去卷积质量来给出准确和可解释的质量。在治疗性抗体方面，新算法促进了延伸、截断和Fab糖基化的分析。该算法便于使用天然质谱学对蛋白质和蛋白质组件进行定性和定量分析。
Charge deconvolution infers the mass from mass over charge (m/z) measurements in electrospray ionization mass spectra. When applied over a wide input m/z or broad target mass range, charge-deconvolution algorithms can produce artifacts, such as false masses at one-half or one-third of the correct mass. Indeed, a maximum entropy term in the objective function of MaxEnt, the most commonly used charge deconvolution algorithm, favors a deconvolved spectrum with many peaks over one with fewer peaks. Here we describe a new “parsimonious” charge deconvolution algorithm that produces fewer artifacts. The algorithm is especially well-suited to high-resolution native mass spectrometry of intact glycoproteins and protein complexes. Deconvolution of native mass spectra poses special challenges due to salt and small molecule adducts, multimers, wide mass ranges, and fewer and lower charge states. We demonstrate the performance of the new deconvolution algorithm on a range of samples. On the heavily glycosylated plasma properdin glycoprotein, the new algorithm could deconvolve monomer and dimer simultaneously and, when focused on the m/z range of the monomer, gave accurate and interpretable masses for glycoforms that had previously been analyzed manually using m/z peaks rather than deconvolved masses. On therapeutic antibodies, the new algorithm facilitated the analysis of extensions, truncations, and Fab glycosylation. The algorithm facilitates the use of native mass spectrometry for the qualitative and quantitative analysis of protein and protein assemblies.
登录
查看更多内容
DOI：
10.1007/s13361-015-1235-6
发表时间：
2015-12
影响因子：
3.2
作者：
Lu, Jonathan;Trnka, Michael J.;Roh, Soung-Hun;Robinson, Philip J. J.;Shiau, Carrie;Fujimori, Danica Galonic;Chiu, Wah;Burlingame, Alma L.;Guan, Shenheng
通讯作者：
Guan, Shenheng
DOI：
10.1385/1-59259-045-4:239
发表时间：
2000-01-01
期刊：
MASS SPECTROMETRY OF PROTEINS AND PEPTIDES
影响因子：
--
作者：
Krutchinsky, AN;Ayed, A;Standing, KG
通讯作者：
Standing, KG
影响因子：
18.2
作者：
Loessl, Philip;Brunner, Andrea M.;Heck, Albert J. R.
通讯作者：
Heck, Albert J. R.
影响因子：
2.9
作者：
Chevreux, Guillaume;Tilly, Nolwenn;Bihoreau, Nicolas
通讯作者：
Bihoreau, Nicolas
影响因子：
48
作者：
Rose, Rebecca J.;Damoc, Eugen;Heck, Albert J. R.
通讯作者：
Heck, Albert J. R.