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

激光-固体相互作用的最新结果表明，有一种简便的方法可以将大分子推进到气相中，而几乎不会降解。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，甚至是部分方法，如共结晶或离子形成。该提案计划研究产生样品晶体、激发、喷射和电离浓缩分子样品中的分子的机制的化学和物理，重点是蛋白质和核酸的MALDI实验。将探索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200 ps，HD为1 ns至100 ns)和可访问信息(分子与主体属性)方面相辅相成。大的生物分子很难或不可能蒸发，因为它们往往在达到足够高的温度之前分解。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)，它通过将大分子嵌入到易于蒸发的基质中来解决这个问题，这种基质可以被脉冲激光辐射激发。MALDI方法在测定大分子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，但对基本过程的理解是滞后的。该提案计划探索产生样品晶体、激发、喷射和电离浓缩分子样品的分子的化学和物理机制，重点是蛋白质和核酸的MALDI实验。更好地理解所涉及的基本现象将有助于将MALDI的能力扩展到更大一组重要的生物分子。

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.