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

激光与固体相互作用的最新研究结果表明， 一种将大分子推进到气相中的简便方法， 或者没有降解。 这个特别令人兴奋的新方法， 基质辅助激光解吸电离（MALDI），具有巨大的 扩大了高分子量光谱的质量范围 生物分子 目前还没有足够的理论来解释整个 方法，或者甚至是它的一部分，如共结晶或离子形成。 该提案计划研究机制的化学和物理学 产生样品晶体，激发，弹出， 从浓缩的分子样品中提取分子，重点是MALDI 蛋白质和核酸的实验。 弹射的两个极限 过程将探讨：流体力学（HD）的限制和分子 动态（MD）极限。 这两种描述在术语上是相辅相成的 时间尺度（MD为200 ps，HD为1 ns至100 ns）， 信息（分子与体积特性）。 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。 最准确的 然而，光谱方法依赖于气相分子。一个最近 发现的现象，称为基质辅助激光解吸/电离 （MALDI），通过将大分子嵌入到 一种可被脉冲激光激发的易蒸发基质， 辐射 MALDI方法提供了前所未有的准确性， 大蛋白质和其他生物分子的分子量测定。 尽管这种方法有很大的好处， 基础进程滞后。该提案计划探索 产生样品晶体的机制的化学和物理学， 从凝聚的分子中激发、喷射和释放分子 样品，重点是蛋白质和核酸的MALDI实验 acids. 提高对所涉及的基本现象的理解将有助于 将MALDI的功能扩展到更大的重要群体， 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.