Modeling of Matrix-Assisted Laser Desorption Ionization of Proteins and Nucleic Acids

蛋白质和核酸的基质辅助激光解吸电离建模

• 批准号: 9523413
• 负责人: Akos Vertes
• 金额: $ 24.43万
• 依托单位: George Washington University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-12-15 至 1999-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9523413&HistoricalAwards=false
• 关键词: Modeling; Matrix; Assisted; Laser; Desorption

Recent results in laser-solid interactions indicate that there is a convenient way to propel large molecules into the gas phase with little or no degradation. This particularly exciting new method, matrix-assisted laser desorption ionization (MALDI), has enormously expanded the mass range for the spectroscopy of high molecular weight biomolecules. No adequate theory is yet available to explain the entire method, or even parts of it like co-crystallization or ion formation. The proposal plans to study the chemistry and physics of the mechanisms that produce the sample crystals, energize, eject, and ionize the molecules from condensed molecular samples with emphasis on the MALDI experiments on proteins and nucleic acids. Two limits of the ejection process will be explored: the hydrodynamic (HD) limit and the molecular dynamic (MD) limit. The two descriptions complement each other in terms of time scales (200 ps for MD vs. 1 ns to 100 ns for HD) and accessible information (molecular vs. bulk properties). Large biomolecules are hard or impossible to evaporate since they tend to decompose before reaching high-enoughtemperature. The most accurate spectroscopic methods, however, rely on gas phase molecules. A recently discovered phenomenon, called matrix-assisted laser desorption/ionization (MALDI), gets around this problem by embedding the large molecules into an easy-to-evaporate matrix that can be excited by pulsed laser radiation. The MALDI method has provided unprecedented accuracy in the molecular mass determination of large proteins and other biomolecules. Despite the great benefits of this method, understanding of the underlying processes is lagging behind. The proposal plans to explore the chemistry and physics of the mechanisms that produce the sample crystals, energize, eject, and ionize the molecules from condensed molecular samples with emphasis on the MALDI experiments on proteins and nucleic acids. Improved understanding of the basic phenomena involved will help to extend the capabilities of MALDI for a larger group of important biomolecules.

激光-固体相互作用的最新结果表明，有一种方便的方法可以将大分子推进气相，而很少或没有降解。这种特别令人兴奋的新方法，基质辅助激光解吸电离（MALDI），极大地扩展了高分子量生物分子光谱的质量范围。目前还没有足够的理论来解释整个方法，甚至是其中的一部分，比如共结晶或离子形成。该提案计划研究产生样品晶体的化学和物理机制，从浓缩分子样品中激发，弹出和电离分子，重点是蛋白质和核酸的MALDI实验。将探讨喷射过程的两个极限：流体动力学（HD）极限和分子动力学（MD）极限。这两种描述在时间尺度（MD为200ps， HD为1ns至100ns）和可访问信息（分子与体性质）方面相互补充。大的生物分子很难或不可能蒸发，因为它们在达到足够高的温度之前往往会分解。然而，最精确的光谱方法依赖于气相分子。最近发现的一种现象，称为基质辅助激光解吸/电离（MALDI），通过将大分子嵌入易于蒸发的基质中，可以通过脉冲激光辐射激发，从而解决了这个问题。MALDI方法在测定大蛋白质和其他生物分子的分子质量方面提供了前所未有的准确性。尽管这种方法有很大的好处，但对潜在过程的理解是滞后的。该提案计划探索产生样品晶体的化学和物理机制，从浓缩分子样品中激发，弹出和电离分子，重点是蛋白质和核酸的MALDI实验。对所涉及的基本现象的更好理解将有助于将MALDI的能力扩展到更大的重要生物分子群。