Mohimani Hosein, Kim Sangtae, Pevzner Pavel A
Department of Electrical and Computer Engineering and ‡Department of Computer Science and Engineering, University of California-San Diego , San Diego, California 92093.
J Proteome Res. 2013 Apr 5;12(4):1560-8. doi: 10.1021/pr300453t. Epub 2013 Mar 8.
While nonlinear peptide natural products such as Vancomycin and Daptomycin are among the most effective antibiotics, the computational techniques for sequencing such peptides are still in their infancy. Previous methods for sequencing peptide natural products are based on Nuclear Magnetic Resonance spectroscopy and require large amounts (milligrams) of purified materials. Recently, development of mass spectrometry-based methods has enabled accurate sequencing of nonlinear peptide natural products using picograms of material, but the question of evaluating statistical significance of Peptide Spectrum Matches (PSM) for these peptides remains open. Moreover, it is unclear how to decide whether a given spectrum is produced by a linear, cyclic, or branch-cyclic peptide. Surprisingly, all previous mass spectrometry studies overlooked the fact that a very similar problem has been successfully addressed in particle physics in 1951. In this work, we develop a method for estimating statistical significance of PSMs defined by any peptide (including linear and nonlinear). This method enables us to identify whether a peptide is linear, cyclic, or branch-cyclic, an important step toward identification of peptide natural products.
虽然诸如万古霉素和达托霉素等非线性肽天然产物是最有效的抗生素之一，但用于此类肽测序的计算技术仍处于起步阶段。以前用于肽天然产物测序的方法基于核磁共振光谱，需要大量（毫克）纯化材料。最近，基于质谱的方法的发展使得能够使用皮克级别的材料对非线性肽天然产物进行准确测序，但对于这些肽的肽谱匹配（PSM）评估统计显著性的问题仍然悬而未决。此外，尚不清楚如何确定给定的谱是由线性、环状还是分支环状肽产生的。令人惊讶的是，之前所有的质谱研究都忽略了一个事实，即一个非常相似的问题早在1951年就在粒子物理学中得到了成功解决。在这项工作中，我们开发了一种方法来估计由任何肽（包括线性和非线性）定义的PSM的统计显著性。这种方法使我们能够识别肽是线性、环状还是分支环状的，这是鉴定肽天然产物的重要一步。
